CN116819093A - Electromagnetic radiation sensitive nerve cell related serological marker and application thereof - Google Patents
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Abstract
本发明公开了一种电磁辐射敏感的神经细胞相关血清学标志物,为神经元烯醇化酶NSE、S100β蛋白、脑源性神经营养因子BDNF和血管内皮生长因子VEGF。本发明还公开了电磁辐射敏感的神经细胞相关血清学标志物在制备诊断电磁辐射损伤疾病的试剂盒或设备中的应用。本发明首次提出联合应用中枢神经生化血清学指标NSE、S100β、BDNF、VEGF,采用放射免疫分析的方法,评价电磁辐射脑损伤效应,提供了一种用于电磁辐射脑损伤效应评价的血清学敏感指标及其评价方法。
The invention discloses an electromagnetic radiation-sensitive nerve cell-related serological marker, which is neuronal enolase NSE, S100β protein, brain-derived neurotrophic factor BDNF and vascular endothelial growth factor VEGF. The invention also discloses the use of electromagnetic radiation-sensitive nerve cell-related serological markers in preparing kits or equipment for diagnosing electromagnetic radiation damage diseases. The present invention proposes for the first time the joint application of central nervous system biochemical serological indicators NSE, S100β, BDNF, and VEGF, and the use of radioimmunoassay methods to evaluate the brain damage effects of electromagnetic radiation, and provides a serological sensitivity for the evaluation of the brain damage effects of electromagnetic radiation. Indicators and their evaluation methods.
Description
技术领域Technical field
本发明属于电磁辐射损伤技术领域,涉及电磁辐射敏感的神经细胞相关血清学标志物及其应用。The invention belongs to the technical field of electromagnetic radiation damage and relates to electromagnetic radiation-sensitive nerve cell-related serological markers and their applications.
背景技术Background technique
随着电子信息技术的迅速发展及各种电子设备的广泛应用,人类生存空间的电磁辐射日益增强,电磁场对生命活动及人类健康的影响逐渐引起人们的重视。其中,微波(microwave,MW)在无线通讯、感应加热、家用电器、军事和医疗等领域应用均较广泛,尤其是手机、Wi-Fi等电子设备的普及应用,使得微波辐射与人类生活密切相关。因此,微波辐射的生物学效应及其卫生防护已成为生命科学领域的研究热点之一。With the rapid development of electronic information technology and the widespread use of various electronic equipment, electromagnetic radiation in human living spaces is increasing day by day, and the impact of electromagnetic fields on life activities and human health has gradually attracted people's attention. Among them, microwave (MW) is widely used in wireless communications, induction heating, household appliances, military and medical fields, especially the popularization of electronic devices such as mobile phones and Wi-Fi, making microwave radiation closely related to human life. . Therefore, the biological effects of microwave radiation and its health protection have become one of the research hotspots in the field of life sciences.
流行病学调查显示,从事电磁环境作业人员或长期低剂量微波辐射人员可出现注意力分散、失眠多梦、记忆力减退等植物神经症状,以及内分泌功能紊乱、免疫力下降、女性生理周期紊乱或男性生殖功能下降等。由于电磁辐射生物学效应的分子机理尚未阐明,关于电磁辐射对生物体作用敏感的分子靶标亦未明确,因而迄今缺乏用于电磁辐射生物学效应评估的敏感生物学指标及其评价方法。Epidemiological surveys show that people who work in electromagnetic environments or who are exposed to long-term low-dose microwave radiation may suffer from autonomic symptoms such as distraction, insomnia and dreaminess, and memory loss, as well as endocrine dysfunction, decreased immunity, and menstrual cycle disorders in women or men. Decreased reproductive function, etc. Since the molecular mechanism of the biological effects of electromagnetic radiation has not yet been elucidated, and the molecular targets that are sensitive to the effects of electromagnetic radiation on living organisms have not been clarified, sensitive biological indicators and evaluation methods for evaluating the biological effects of electromagnetic radiation are currently lacking.
发明内容Contents of the invention
本发明的一个目的是解决至少上述问题和/或缺陷,并提供至少后面将说明的优点。It is an object of the present invention to solve at least the above problems and/or disadvantages and to provide at least the advantages to be explained below.
神经元烯醇化酶(neuron-specific enolase,NSE)是神经元和神经内分泌细胞分泌的一种酸性蛋白酶,参与神经细胞糖酵解,对于维持脑组织的生理功能必不可少。S100β是一种浓度依赖性的脑内特异性蛋白,主要表达于星形胶质细胞、少突胶质细胞和施万细胞,在神经细胞增殖、分化、能量代谢、细胞膜结构、抗氧化损伤及细胞凋亡信号传导等过程中具有重要调控作用。在生理浓度即pmol或nmol水平,S100β具有神经营养作用;在μmol水平,S100β具有神经毒性作用,可诱导促炎细胞因子释放,通过一氧化氮依赖途径诱导神经元细胞死亡,并可通过钙依赖途径诱导神经系统退行性变。Neuron-specific enolase (NSE) is an acidic protease secreted by neurons and neuroendocrine cells. It participates in glycolysis of nerve cells and is essential for maintaining the physiological functions of brain tissue. S100β is a concentration-dependent brain-specific protein mainly expressed in astrocytes, oligodendrocytes and Schwann cells. It plays a role in nerve cell proliferation, differentiation, energy metabolism, cell membrane structure, antioxidant damage and It plays an important regulatory role in apoptosis signaling and other processes. At physiological concentrations, that is, pmol or nmol levels, S100β has a neurotrophic effect; at μmol levels, S100β has a neurotoxic effect, inducing the release of pro-inflammatory cytokines, inducing neuronal cell death through a nitric oxide-dependent pathway, and can induce neuronal cell death through a calcium-dependent Pathways induce degeneration of the nervous system.
NSE和S100β蛋白是特异性存在于神经元或神经胶质细胞内的蛋白酶,各种原因导致脑损伤时,神经细胞受损,细胞膜通透性增加,血脑屏障破坏,NSE和S100β通过血脑屏障进入外周血液循环,导致血清NSE和S100β浓度升高。因此,可将NSE和S100β作为反映脑损伤的特异性血清标志物,用于中枢神经系统疾病的病情监测、预后判断和疗效观察等方面,是诊断、预后、甚至治疗的理想中枢神经生化指标。NSE and S100β proteins are proteases that specifically exist in neurons or glial cells. When brain injury occurs due to various reasons, nerve cells are damaged, cell membrane permeability increases, and the blood-brain barrier is destroyed. NSE and S100β pass through the blood brain. Barrier into peripheral blood circulation, resulting in increased serum NSE and S100β concentrations. Therefore, NSE and S100β can be used as specific serum markers reflecting brain injury, and can be used for condition monitoring, prognosis judgment and efficacy observation of central nervous system diseases. They are ideal central nervous system biochemical indicators for diagnosis, prognosis and even treatment.
脑源性神经营养因子(brain-derived neurotrophic factor,BDNF)是神经营养因子家族的主要成员之一,主要由神经元和星形胶质细胞分泌,以海马、杏仁核和皮质等脑区分布最为丰富。对神经元生存、生长和维持至关重要,并参与情绪、认知功能的调节,与早老性痴呆、急性神经系统损伤等疾病的发生和发展密切相关。血管内皮生长因子(vascularendothelial growth factor,VEGF)是一种高度特异性的促血管内皮细胞生长因子,可特异性增强血管通透性、促进新生血管形成、参与神经保护等。当神经元损伤发生时,VEGF可促进神经轴突生长及神经细胞存活。Brain-derived neurotrophic factor (BDNF) is one of the main members of the neurotrophic factor family. It is mainly secreted by neurons and astrocytes and is most distributed in brain areas such as the hippocampus, amygdala, and cortex. Rich. It is essential for the survival, growth and maintenance of neurons, and is involved in the regulation of emotions and cognitive functions. It is closely related to the occurrence and development of diseases such as Alzheimer's disease and acute nervous system injury. Vascular endothelial growth factor (VEGF) is a highly specific pro-vascular endothelial cell growth factor that can specifically enhance vascular permeability, promote neovascularization, and participate in neuroprotection. When neuronal damage occurs, VEGF can promote nerve axon growth and nerve cell survival.
关于电磁辐射对血清NSE、S100β、BDNF、VEGF影响的研究报道尚属空白,仅见少数研究报道电磁辐射对脑组织中NSE、BDNF表达的影响。由于血清学检测采样方便、灵敏快速、结果可重复性好,因而血清学标志物检测具有较高的临床应用价值。目前仍缺乏电磁辐射脑损伤敏感的血清学标志物。There are still no research reports on the effects of electromagnetic radiation on serum NSE, S100β, BDNF, and VEGF. There are only a few studies reporting the effects of electromagnetic radiation on the expression of NSE and BDNF in brain tissue. Serological marker detection has high clinical application value due to its convenient sampling, rapid sensitivity, and good reproducibility of results. There is still a lack of sensitive serological markers for electromagnetic radiation brain damage.
为此,本发明基于两种不同频段的微波辐射分别建立动物模型,研发适用于电磁辐射脑损伤评价的血清学敏感指标及其检测方法。To this end, the present invention establishes animal models based on microwave radiation in two different frequency bands, and develops serological sensitivity indicators and detection methods suitable for the evaluation of electromagnetic radiation brain damage.
本发明提供的技术方案为:The technical solution provided by the invention is:
第一方面,电磁辐射敏感的神经细胞相关血清学标志物,所述血清学标志物为神经元烯醇化酶NSE、S100β蛋白、脑源性神经营养因子BDNF和血管内皮生长因子VEGF。The first aspect is electromagnetic radiation-sensitive nerve cell-related serological markers. The serological markers are neuronal enolase NSE, S100β protein, brain-derived neurotrophic factor BDNF and vascular endothelial growth factor VEGF.
第二方面,一种评价电磁辐射对小鼠神经细胞损伤的动物模型的构建方法,包括如下步骤:In the second aspect, a method for constructing an animal model to evaluate the damage of electromagnetic radiation to mouse nerve cells includes the following steps:
选取小鼠,随机分为微波辐射组和假辐射组,将微波辐射组小鼠置于透明带孔辐射盒中,将所述辐射盒置于微波暗室内可旋转的辐射台,自上而下辐射,假辐射组进行同等条件伪辐射,得到评价电磁辐射对小鼠神经细胞损伤的动物模型。Mice were selected and randomly divided into a microwave radiation group and a sham radiation group. The mice in the microwave radiation group were placed in a transparent radiation box with holes. The radiation box was placed on a rotatable radiation table in a microwave darkroom, from top to bottom. The sham radiation group underwent sham radiation under the same conditions to obtain an animal model for evaluating the damage of electromagnetic radiation to mouse nerve cells.
优选的是,所述的评价电磁辐射对小鼠神经细胞损伤的动物模型的构建方法中,选取10周龄小鼠,所述小鼠体重为20-24g,雌雄各半,随机分为所述微波辐射组和所述假辐射组。Preferably, in the method of constructing an animal model for evaluating the damage of mouse nerve cells by electromagnetic radiation, 10-week-old mice are selected, and the mice weigh 20-24g, half male and half male, and randomly divided into Microwave radiation group and the pseudo-radiation group.
优选的是,所述的评价电磁辐射对小鼠神经细胞损伤的动物模型的构建方法中,其特征在于,辐射时采用S波段微波辐射或X波段微波辐射,Preferably, the method for constructing an animal model for evaluating electromagnetic radiation damage to mouse nerve cells is characterized in that S-band microwave radiation or X-band microwave radiation is used during radiation,
所述S波段微波辐射条件为:中心频率2.856GHz,平均功率密度8mW/cm2,峰值功率密度200W/cm2,重复频率80Hz,脉冲宽度500ns,SAR值9.4W/kg,辐射时间15min;The S-band microwave radiation conditions are: center frequency 2.856GHz, average power density 8mW/cm 2 , peak power density 200W/cm 2 , repetition frequency 80Hz, pulse width 500ns, SAR value 9.4W/kg, radiation time 15min;
所述X波段微波辐射条件为:中心频率9.375GHz,平均功率密度12mW/cm2,峰值功率密度392W/cm2,重复频率62Hz,脉冲宽度500ns,SAR值9.4W/kg,辐射时间15min。The X-band microwave radiation conditions are: center frequency 9.375GHz, average power density 12mW/cm 2 , peak power density 392W/cm 2 , repetition frequency 62Hz, pulse width 500ns, SAR value 9.4W/kg, radiation time 15min.
第三方面,一种电磁辐射对小鼠神经细胞损伤的评价方法,通过对所述的动物模型进行检测,比较假辐射组和微波辐射组的检测结果,评价电磁辐射对小鼠神经细胞损伤损伤的影响。In the third aspect, a method for evaluating the damage of electromagnetic radiation to mouse nerve cells, by testing the animal model and comparing the test results of the sham radiation group and the microwave radiation group, to evaluate the damage of electromagnetic radiation to mouse nerve cells. Impact.
优选的是,所述的评价方法中,所述检测包括检测神经元烯醇化酶NSE、S100β蛋白、脑源性神经营养因子BDNF和血管内皮生长因子VEGF。Preferably, in the evaluation method, the detection includes detecting neuronal enolase NSE, S100β protein, brain-derived neurotrophic factor BDNF and vascular endothelial growth factor VEGF.
优选的是,所述的评价方法中,所述检测还包括通过新物体识别实验检测小鼠认知行为改变、通过Y迷宫实验检测小鼠空间探索能力改变、通过旷场实验检测小鼠情绪行为改变和通过高架十字迷宫实验检测小鼠情绪行为改变。Preferably, in the evaluation method, the detection also includes detecting changes in cognitive behavior of mice through a new object recognition experiment, detecting changes in spatial exploration ability of mice through a Y maze experiment, and detecting emotional behaviors of mice through an open field experiment. Changes and detection of emotional behavioral changes in mice through the elevated plus maze test.
第四方面,包含能够检测所述的电磁辐射敏感的神经细胞相关血清学标志物的试剂的试剂盒。The fourth aspect is a kit comprising a reagent capable of detecting the electromagnetic radiation-sensitive nerve cell-related serological markers.
第五方面,所述的电磁辐射敏感的神经细胞相关血清学标志物或所述的动物模型在制备诊断电磁辐射神经细胞损伤疾病的试剂盒或设备中的应用。The fifth aspect is the use of the electromagnetic radiation-sensitive nerve cell-related serological markers or the animal model in the preparation of kits or equipment for diagnosing electromagnetic radiation nerve cell damage diseases.
本发明至少包括以下有益效果:The present invention at least includes the following beneficial effects:
本发明基于两种不同频段的微波辐射分别建立动物模型,研发适用于电磁辐射脑损伤评价的血清学敏感指标及其检测方法,首次提出联合应用中枢神经生化血清学指标NSE、S100β、BDNF、VEGF,采用放射免疫分析的方法,评价电磁辐射脑损伤效应。从而提供了一种用于电磁辐射脑损伤效应评价的血清学敏感指标及其评价方法。The present invention establishes animal models based on microwave radiation of two different frequency bands, develops serological sensitive indicators and detection methods suitable for the evaluation of electromagnetic radiation brain damage, and proposes for the first time the joint application of central nervous system biochemical serological indicators NSE, S100β, BDNF, and VEGF. , using radioimmunoassay method to evaluate the brain damage effects of electromagnetic radiation. This provides a serological sensitivity index and its evaluation method for evaluating the brain damage effects of electromagnetic radiation.
本发明的其它优点、目标和特征将部分通过下面的说明体现,部分还将通过对本发明的研究和实践而为本领域的技术人员所理解。Other advantages, objects, and features of the present invention will be apparent in part from the description below, and in part will be understood by those skilled in the art through study and practice of the present invention.
附图说明Description of the drawings
图1展示本发明实施例中微波辐射对小鼠焦虑情绪行为的影响图(旷场实验,n=12),A:S波段微波假辐射组(Control)小鼠旷场实验运动轨迹及其热图示意图;B:S-MW组小鼠旷场实验运动轨迹及其热图示意图;C:S-MW辐射前后小鼠旷场中央区域路程改变;D:S-MW辐射前后小鼠旷场中央区域时间改变;E:X波段微波假辐射组(Control)小鼠旷场实验运动轨迹及其热图示意图;F:X-MW组小鼠旷场实验运动轨迹及其热图示意图;G:X-MW辐射前后小鼠旷场中央区域路程改变;H:X-MW辐射前后小鼠旷场中央区域时间改变;vs辐射前,*示p<0.05,**示p<0.01;vs Control,#示p<0.05。Figure 1 shows the effect of microwave radiation on the anxiety behavior of mice in the embodiment of the present invention (open field experiment, n=12), A: S-band microwave sham radiation group (Control) mouse open field experiment movement trajectory and its heat Schematic diagram; B: The movement trajectory and heat map of mice in the open field experiment of the S-MW group; C: The change in distance in the central area of the open field of mice before and after S-MW radiation; D: The center of the open field of mice before and after S-MW radiation Regional time changes; E: X-band microwave pseudo-radiation group (Control) mice's movement trajectory in the open field experiment and its heat map diagram; F: X-MW group mouse's movement trajectory in the open field experiment and its heat map diagram; G: X -Changes in distance in the central area of the open field in mice before and after MW radiation; H: Changes in time in the central area of the open field in mice before and after X-MW radiation; vs before radiation, * indicates p<0.05, ** indicates p<0.01; vs Control, # Indicates p<0.05.
图2展示本发明实施例微波辐射对小鼠焦虑情绪行为的影响图(高架十字迷宫实验,n=12),A:S波段微波假辐射组(Control)小鼠高架十字迷宫实验运动轨迹及其热图示意图;B:S-MW组小鼠架十字迷宫实验运动轨迹及其热图示意图;C:S-MW辐射前后小鼠进入开放臂路程改变;D:S-MW辐射前后小鼠进入开放臂时间改变。E:X波段微波假辐射组(Control)小鼠高架十字迷宫实验运动轨迹及其热图示意图;F:X-MW辐射组(X-HPM)小鼠高架十字迷宫实验运动轨迹及其热图示意图;G:X-MW辐射前后小鼠进入开放臂路程占比改变;H:X-MW辐射前后小鼠进入开放臂时间占比改变;vs辐射前,*示p<0.05;vs Control,##示p<0.01。Figure 2 shows the effect of microwave radiation on the anxiety behavior of mice according to the embodiment of the present invention (elevated plus maze experiment, n=12). A: S-band microwave sham radiation group (Control) mouse elevated plus maze experiment movement trajectory and its Heat map schematic diagram; B: S-MW group mice's movement trajectory in the plus maze experiment and its heat map schematic diagram; C: Changes in the distance of mice entering the open arm before and after S-MW radiation; D: Mice entering the open arm before and after S-MW radiation Arm time changes. E: The movement trajectory of mice in the X-band microwave sham irradiation group (Control) in the elevated plus maze experiment and its heat map diagram; F: The movement trajectory of mice in the X-MW radiation group (X-HPM) in the elevated plus maze experiment and its heat map diagram ;G: Change in the proportion of mice entering the open arm before and after X-MW radiation; H: Change in the proportion of time mice enter the open arm before and after X-MW radiation; vs before radiation, * indicates p<0.05; vs Control, ## Indicates p<0.01.
图3展示本发明实施例中微波辐射对小鼠认知行为的影响图(Y迷宫实验,n=12),A-B:S-MW组和假辐射组(Control)小鼠Y迷宫实验运动轨迹(A)及其热图(B)示意图;C:S-MW辐射前后小鼠自由交替率改变;D-E:X-MW组和假辐射组(Control)小鼠Y迷宫实验运动轨迹(D)及其热图(E)示意图;F:X-MW辐射前后小鼠自由交替率改变;vs辐射前,*示p<0.05;vsControl,#示p<0.05。Figure 3 shows the effect of microwave radiation on the cognitive behavior of mice in the embodiment of the present invention (Y maze experiment, n=12), AB: Y maze experiment movement trajectories of mice in the S-MW group and the sham radiation group (Control) ( A) Schematic diagram of its heat map (B); C: Changes in the free alternation rate of mice before and after S-MW radiation; DE: Y-maze experimental movement trajectories of mice in the X-MW group and the sham radiation group (Control) (D) and their Heat map (E) Schematic diagram; F: Changes in the free alternation rate of mice before and after X-MW radiation; vs before radiation, * indicates p<0.05; vsControl, # indicates p<0.05.
图4展示本发明实施例中微波辐射对小鼠认知行为的影响图(新物体识别实验,n=12),A-B:S-MW组和假辐射组(Control)小鼠新物体识别实验运动轨迹(A)及其热图(B)示意图;C:S波段微波辐射前后小鼠新物体辨别指数变化;D-E:X-MW组和假辐射组(Control)小鼠新物体识别实验运动轨迹(D)及其热图(E)示意图;F:X-MW辐射前后小鼠新物体辨别指数变化。vs辐射前,*示p<0.05,**示p<0.01;vs Control,#示p<0.05。Figure 4 shows the effect of microwave radiation on cognitive behavior of mice in the embodiment of the present invention (new object recognition experiment, n=12), AB: S-MW group and sham radiation group (Control) mouse new object recognition experiment movement Schematic diagram of the trajectory (A) and its heat map (B); C: Changes in the new object recognition index of mice before and after S-band microwave radiation; DE: Movement trajectories of mice in the X-MW group and sham radiation group (Control) in the new object recognition experiment ( D) Schematic diagram of its heat map (E); F: Changes in mouse novel object discrimination index before and after X-MW radiation. vs before radiation, * indicates p<0.05, ** indicates p<0.01; vs Control, # indicates p<0.05.
图5展示本发明实施例中微波辐射对小鼠血清NSE含量的影响图,A:S-MW辐射后6h(R-6h)和7d(R-7d)小鼠血清NSE含量均显著升高(p<0.01);B:X-MW辐射后6h(R-6h)和7d(R-7d)小鼠血清NSE含量均显著升高(p<0.001);vs Control,**示p<0.01,***示p<0.001。Figure 5 shows the effect of microwave radiation on the serum NSE content of mice in the embodiment of the present invention. A: The serum NSE content of mice increased significantly 6h (R-6h) and 7d (R-7d) after S-MW radiation ( p<0.01); B: The serum NSE content of mice was significantly increased 6h (R-6h) and 7d (R-7d) after X-MW radiation (p<0.001); vs Control, ** indicates p<0.01, *** indicates p<0.001.
图6展示本发明实施例中微波辐射对小鼠血清S100β含量的影响图,A:S-MW辐射后6h(R-6h)和7d(R-7d)小鼠血清S100β含量均显著升高(p<0.01);B:X-MW辐射后6h(R-6h)和7d(R-7d)小鼠血清S100β含量均显著升高(p<0.001);vs Control,**示p<0.01,***示p<0.001。Figure 6 shows the effect of microwave radiation on mouse serum S100β content in the embodiment of the present invention. A: The mouse serum S100β content increased significantly 6h (R-6h) and 7d (R-7d) after S-MW radiation ( p<0.01); B: Serum S100β content in mice was significantly increased 6h (R-6h) and 7d (R-7d) after X-MW radiation (p<0.001); vs Control, ** indicates p<0.01, *** indicates p<0.001.
图7展示本发明实施例中微波辐射对小鼠血清BDNF含量的影响图,A:S-MW辐射后6h(R-6h)和7d(R-7d)小鼠血清BDNF含量均显著降低;B:X-MW辐射后6h(R-6h)和7d(R-7d)小鼠血清BDNF含量均显著降低;vs Control,*示p<0.05,***示p<0.001。Figure 7 shows the effect of microwave radiation on the serum BDNF content of mice in the embodiment of the present invention. A: The serum BDNF content of mice was significantly reduced 6h (R-6h) and 7d (R-7d) after S-MW radiation; B : The serum BDNF content of mice was significantly reduced 6h (R-6h) and 7d (R-7d) after X-MW radiation; vs Control, * indicates p<0.05, *** indicates p<0.001.
图8展示本发明实施例中微波辐射对小鼠血清VEGF含量的影响图,A:S-MW辐射后6h(R-6h)小鼠血清VEGF含量显著降低,但辐射后7d(R-7d)变化不显著;B:X-MW辐射后6h(R-6h)和7d(R-7d)小鼠血清VEGF含量均显著降低;vs Control,***示p<0.001。Figure 8 shows the effect of microwave radiation on the serum VEGF content of mice in the embodiment of the present invention. A: The serum VEGF content of mice significantly decreased 6h after S-MW irradiation (R-6h), but 7d after irradiation (R-7d) The change is not significant; B: The serum VEGF content of mice was significantly reduced 6h (R-6h) and 7d (R-7d) after X-MW radiation; vs Control, *** indicates p<0.001.
具体实施方式Detailed ways
下面结合附图对本发明做进一步的详细说明,以令本领域技术人员参照说明书文字能够据以实施。The present invention will be further described in detail below with reference to the accompanying drawings, so that those skilled in the art can implement it with reference to the text of the description.
应当理解,本文所使用的诸如“具有”、“包含”以及“包括”术语并不排除一个或多个其它元件或其组合的存在或添加。It should be understood that terms such as "having," "comprising," and "including" as used herein do not exclude the presence or addition of one or more other elements or combinations thereof.
需要说明的是,下述实施方案中所述实验方法,如无特殊说明,均为常规方法,所述试剂和材料,如无特殊说明,均可从商业途径获得。It should be noted that the experimental methods described in the following embodiments, unless otherwise specified, are all conventional methods, and the reagents and materials, unless otherwise specified, can be obtained from commercial sources.
本发明提供电磁辐射敏感的神经细胞相关血清学标志物,所述血清学标志物为神经元烯醇化酶NSE、中枢神经系统的特异性蛋白S100β蛋白、脑源性神经营养因子BDNF和血管内皮生长因子VEGF。The present invention provides electromagnetic radiation-sensitive nerve cell-related serological markers. The serological markers are neuronal enolase NSE, central nervous system specific protein S100β protein, brain-derived neurotrophic factor BDNF and vascular endothelial growth. Factor VEGF.
本发明提供一种评价电磁辐射对小鼠神经细胞损伤的动物模型的构建方法,包括如下步骤:The invention provides a method for constructing an animal model for evaluating the damage of electromagnetic radiation to mouse nerve cells, which includes the following steps:
选取小鼠,随机分为微波辐射组和假辐射组,将微波辐射组小鼠置于透明带孔辐射盒中,将所述辐射盒置于微波暗室内可旋转的辐射台,自上而下辐射,假辐射组进行同等条件伪辐射,得到评价电磁辐射对小鼠神经细胞损伤的动物模型。Mice were selected and randomly divided into a microwave radiation group and a sham radiation group. The mice in the microwave radiation group were placed in a transparent radiation box with holes. The radiation box was placed on a rotatable radiation table in a microwave darkroom, from top to bottom. The sham radiation group underwent sham radiation under the same conditions to obtain an animal model for evaluating the damage of electromagnetic radiation to mouse nerve cells.
在上述方案中,作为优选,选取10周龄小鼠,所述小鼠体重为20-24g,雌雄各半,随机分为所述微波辐射组和所述假辐射组。In the above scheme, as a preferred option, 10-week-old mice with a weight of 20-24g, half male and half male, are randomly divided into the microwave irradiation group and the sham irradiation group.
在上述方案中,作为优选,辐射时采用S波段微波辐射或X波段微波辐射,In the above solution, as a preferred method, S-band microwave radiation or X-band microwave radiation is used for radiation.
所述S波段微波辐射条件为:中心频率2.856GHz,平均功率密度8mW/cm2,峰值功率密度200W/cm2,重复频率80Hz,脉冲宽度500ns,SAR值9.4W/kg,辐射时间15min;The S-band microwave radiation conditions are: center frequency 2.856GHz, average power density 8mW/cm 2 , peak power density 200W/cm 2 , repetition frequency 80Hz, pulse width 500ns, SAR value 9.4W/kg, radiation time 15min;
所述X波段微波辐射条件为:中心频率9.375GHz,平均功率密度12mW/cm2,峰值功率密度392W/cm2,重复频率62Hz,脉冲宽度500ns,SAR值9.4W/kg,辐射时间15min。The X-band microwave radiation conditions are: center frequency 9.375GHz, average power density 12mW/cm 2 , peak power density 392W/cm 2 , repetition frequency 62Hz, pulse width 500ns, SAR value 9.4W/kg, radiation time 15min.
S波段和X波段微波辐射可引起焦虑情绪改变和认知功能损害,中枢神经生化血清学指标NSE、S100β含量显著升高,而血清神经营养因子BDNF、VEGF含量显著下降,表明微波辐射可引起神经细胞受损,参与神经保护的细胞因子BDNF、VEGF减少,细胞膜通透性增加,NSE、S100β释放增多,血脑屏障破坏,血清NSE、S100β含量升高,血清神经营养因子BDNF、VEGF含量降低。另一方面,X-MW较S-MW辐射小鼠血清NSE、S100β、BDNF、VEGF水平变化更为明显。以上提示,电磁辐射所致中枢神经生化血清学指标变化与辐射频率呈正相关,即辐射频率越大,中枢神经生化血清学指标水平变化越大。S-band and Cells are damaged, the cytokines BDNF and VEGF involved in neuroprotection are reduced, the cell membrane permeability is increased, the release of NSE and S100β is increased, the blood-brain barrier is destroyed, the levels of serum NSE and S100β are increased, and the levels of serum neurotrophic factors BDNF and VEGF are reduced. On the other hand, the changes in serum NSE, S100β, BDNF, and VEGF levels in X-MW irradiated mice were more obvious than those in S-MW irradiated mice. The above suggests that changes in central nervous system biochemical serological indicators caused by electromagnetic radiation are positively correlated with radiation frequency, that is, the greater the radiation frequency, the greater the changes in central nervous system biochemical serological indicator levels.
本发明还提供一种电磁辐射对小鼠神经细胞损伤损伤的评价方法,通过对所述的动物模型进行检测,比较假辐射组和微波辐射组的检测结果,评价电磁辐射对小鼠神经细胞损伤损伤的影响。The present invention also provides a method for evaluating the damage of electromagnetic radiation to mouse nerve cells. By detecting the animal model and comparing the detection results of the sham radiation group and the microwave radiation group, the damage of electromagnetic radiation to mouse nerve cells is evaluated. Effects of damage.
在上述方案中,作为优选,所述检测包括检测神经元烯醇化酶NSE、S100β蛋白、脑源性神经营养因子BDNF和血管内皮生长因子VEGF。在将所述微波辐射组和所述假辐射组的血清神经元烯醇化酶NSE、S100β蛋白、脑源性神经营养因子BDNF和血管内皮生长因子VEGF含量分别一一进行比较,若所述微波辐射组的神经元烯醇化酶NSE、S100β蛋白的含量显著升高,且脑源性神经营养因子BDNF和血管内皮生长因子VEGF含量显著下降,则评价电磁辐射对小鼠神经细胞造成损伤。In the above scheme, preferably, the detection includes detection of neuronal enolase NSE, S100β protein, brain-derived neurotrophic factor BDNF and vascular endothelial growth factor VEGF. After comparing the serum neuronal enolase NSE, S100β protein, brain-derived neurotrophic factor BDNF and vascular endothelial growth factor VEGF contents of the microwave irradiation group and the sham irradiation group one by one, if the microwave irradiation The levels of neuronal enolase NSE and S100β protein in the group were significantly increased, and the levels of brain-derived neurotrophic factor BDNF and vascular endothelial growth factor VEGF were significantly decreased, indicating that the damage caused by electromagnetic radiation to mouse nerve cells was evaluated.
在上述方案中,作为优选,所述检测还包括通过新物体识别实验检测小鼠认知行为改变、通过Y迷宫实验检测小鼠空间探索能力改变、通过旷场实验检测小鼠情绪行为改变和通过高架十字迷宫实验检测小鼠情绪行为改变。S波段和X波段微波辐射均可导致小鼠旷场中央区域活动时间和中央区域活动路程显著减少,提示S波段和X波段微波辐射可引起小鼠焦虑样行为发生,导致情绪行为异常。S波段和X波段微波辐射均可导致小鼠进入开放臂路程和时间路程显著减少,进一步提示S波段和X波段微波辐射可引起小鼠焦虑样行为发生,导致情绪行为异常。S波段和X波段微波辐射均可导致小鼠新物体辨别指数显著降低,提示S波段和X波段微波辐射可引起小鼠事件记忆能力下降,从而导致认知功能障碍。In the above scheme, preferably, the detection also includes detecting changes in the cognitive behavior of mice through a new object recognition experiment, detecting changes in the spatial exploration ability of mice through a Y maze experiment, detecting changes in the emotional behavior of mice through an open field experiment, and detecting changes in the mouse's emotional behavior through a Y-maze experiment. Elevated plus maze test to detect emotional and behavioral changes in mice. Both S-band and X-band microwave radiation can cause a significant reduction in the activity time and distance of activity in the central area of the open field in mice, suggesting that S-band and Both S-band and X-band microwave radiation can cause the distance and time distance of mice to enter the open arm to be significantly reduced, further suggesting that S-band and Both S-band and X-band microwave radiation can cause a significant decrease in the novel object discrimination index of mice, suggesting that S-band and
本发明还提供包含能够检测所述的电磁辐射敏感的神经细胞相关血清学标志物的试剂的试剂盒。The present invention also provides a kit comprising a reagent capable of detecting the electromagnetic radiation-sensitive nerve cell-related serological markers.
本发明还提供所述的电磁辐射敏感的神经细胞相关血清学标志物或所述的动物模型在制备诊断电磁辐射神经细胞损伤疾病的试剂盒或设备中的应用。The present invention also provides the use of the electromagnetic radiation-sensitive nerve cell-related serological markers or the animal model in preparing kits or equipment for diagnosing electromagnetic radiation nerve cell damage diseases.
为使本领域技术更好地理解本发明的技术方案,现提供如下的实施例进行说明:In order for those skilled in the art to better understand the technical solutions of the present invention, the following examples are provided for illustration:
1.材料与方法1.Materials and methods
1.1电磁辐射动物模型建立1.1 Establishment of electromagnetic radiation animal model
选取10周龄C57 BL/6N小鼠,体重22±2g,雌雄各半,随机分为微波辐射组和假辐射组。采用军事医学研究院自建高功率微波(high power microwave,HPM)辐射模拟源,小鼠置于透明带孔有机玻璃盒中,将辐射盒置于微波暗室内可旋转的辐射台,微波源自上而下均匀辐射,假辐射组进行同等条件伪辐射。10-week-old C57 BL/6N mice, weighing 22±2g, half male and half female, were randomly divided into microwave irradiation group and sham irradiation group. A high power microwave (HPM) radiation simulation source built by the Military Medical Research Institute was used. The mice were placed in a transparent perforated plexiglass box, and the radiation box was placed on a rotatable radiation table in the microwave darkroom. The microwaves were generated from Radiation is uniform from top to bottom, and the pseudo-radiation group performs pseudo-radiation under the same conditions.
S波段微波(S-MW)辐射条件如下:中心频率2.856GHz,平均功率密度8mW/cm2,峰值功率密度200W/cm2,重复频率80Hz,脉冲宽度500ns,SAR值9.4W/kg,辐射时间15min。S-band microwave (S-MW) radiation conditions are as follows: center frequency 2.856GHz, average power density 8mW/cm 2 , peak power density 200W/cm 2 , repetition frequency 80Hz, pulse width 500ns, SAR value 9.4W/kg, radiation time 15 minutes.
X波段微波(X-MW)辐射条件如下:中心频率9.375GHz,平均功率密度12mW/cm2,峰值功率密度392W/cm2,重复频率62Hz,脉冲宽度500ns,SAR值9.4W/kg,辐射时间15min。X-band microwave (X-MW) radiation conditions are as follows: center frequency 9.375GHz, average power density 12mW/cm 2 , peak power density 392W/cm 2 , repetition frequency 62Hz, pulse width 500ns, SAR value 9.4W/kg, radiation time 15 minutes.
1.2新物体识别实验检测小鼠认知行为改变1.2 New object recognition experiment to detect changes in cognitive behavior of mice
采用40cm X 40cm X 40cm白色旷场箱,旷场箱内并排放入两个不同颜色的4cmX4cm X 4cm方形物体,木块距离旷场箱壁最近距离为12cm。首先将小鼠置于旷场箱中央,自由活动5min后放回笼内。间隔1h后将其中一个物体更换为不同颜色的球形物体,并放置于另一个物体的对角线位置。利用自动视频跟踪和Anymaze行为学分析软件,记录小鼠5min内探索新旧物体的时间,并计算新物体辨别指数(T新物体–T旧物体)/(T新物体+T旧物体)。分别于微波辐射前和辐射后7d进行检测,分析小鼠在开阔环境对新物体的识别和探索能力,评价其认知行为改变。Use a 40cm X 40cm X 40cm white open field box. Two 4cm First, place the mouse in the center of the open field box, move freely for 5 minutes and then return it to the cage. After an interval of 1 hour, replace one of the objects with a spherical object of a different color and place it diagonally to the other object. Using automatic video tracking and Anymaze behavioral analysis software, record the time the mice spent exploring new and old objects within 5 minutes, and calculate the new object discrimination index (T new object – T old object )/(T new object + T old object ). Tests were conducted before and 7 days after microwave radiation to analyze the mice's ability to recognize and explore new objects in an open environment and evaluate their cognitive behavioral changes.
1.3Y迷宫实验检测小鼠空间探索能力改变1.3Y maze experiment to detect changes in spatial exploration ability of mice
采用臂长30cm,臂宽8cm,臂高15cm的Y迷宫,实验前一天将动物置于Y迷宫中自由探索适应30min。实验时将动物置于Y迷宫中央区域,利用自动视频跟踪和Anymaze行为学分析软件,记录小鼠8min内活动轨迹,并计算自由交替率(连续访问三条臂的次数/访问总次数-2)。分别于微波辐射前和辐射后7d进行检测,评价小鼠空间探索记忆能力改变。A Y maze with an arm length of 30 cm, an arm width of 8 cm, and an arm height of 15 cm was used. The day before the experiment, the animals were placed in the Y maze to freely explore and adapt for 30 minutes. During the experiment, the animals were placed in the central area of the Y maze. Automatic video tracking and Anymaze behavioral analysis software were used to record the activity trajectories of the mice within 8 minutes, and the free alternation rate was calculated (number of consecutive visits to three arms/total number of visits - 2). Detection was conducted before and 7 days after microwave irradiation to evaluate the changes in the mice's spatial exploration and memory ability.
1.4旷场实验检测小鼠情绪行为改变1.4 Open field experiment to detect changes in emotional behavior of mice
采用40cm X 40cm白色旷场箱,将动物置于旷场箱中央,利用自动视频跟踪和Anymaze行为学分析软件,记录小鼠5min内的活动轨迹及中央区域活动路程和时间,检测小鼠在开阔环境的自主探究及焦虑样行为。分别于微波辐射前和辐射后7d进行检测,评价小鼠焦虑情绪行为改变。Use a 40cm Independent exploration of the environment and anxiety-like behavior. Detection was carried out before and 7 days after microwave radiation to evaluate the changes in anxiety and behavior of the mice.
1.5高架十字迷宫实验检测小鼠情绪行为改变1.5 Elevated plus maze experiment to detect changes in emotional behavior of mice
采用高50cm、宽6cm、臂长30cm、闭合臂高15cm的高架十字迷宫,首先将小鼠面向开放臂置于中央区域,利用自动视频跟踪和Anymaze行为学分析软件,记录小鼠5min内进入开放臂的路程及时间。分别于微波辐射前和辐射后7d进行检测,分析小鼠主动探索及焦虑情绪行为,评价微波辐射对小鼠情绪行为的影响。An elevated plus maze with a height of 50cm, a width of 6cm, an arm length of 30cm, and a closed arm height of 15cm was used. First, the mouse was placed in the central area facing the open arm. Automatic video tracking and Anymaze behavioral analysis software were used to record the mouse entering the open arm within 5 minutes. arm distance and time. Detection was conducted before and 7 days after microwave radiation to analyze the mice's active exploration and anxiety behavior, and to evaluate the impact of microwave radiation on the mice's emotional behavior.
1.6放射免疫分析法检测血清NSE、S100β、BDNF、VEGF含量1.6 Radioimmunoassay to detect serum NSE, S100β, BDNF, and VEGF levels
分别于微波辐射后6h和7d,小鼠经0.5%戊巴比妥钠腹腔注射(50mg/kg)麻醉后,经腹主动脉取血,离心收集血清,采用放射免疫分析法,参照NSE、S100β、BDNF、VEGF检测试剂盒说明书,利用γ放射免疫计数器检测血清NSE、S100β、BDNF、VEGF含量。At 6 hours and 7 days after microwave irradiation, the mice were anesthetized by intraperitoneal injection of 0.5% sodium pentobarbital (50 mg/kg). Blood was collected from the abdominal aorta, and serum was collected by centrifugation. Radioimmunoassay was used with reference to NSE and S100β. , BDNF, VEGF detection kit instructions, use a gamma radiation immune counter to detect serum NSE, S100β, BDNF, and VEGF levels.
1.7统计学分析1.7 Statistical analysis
实验数据以均数±标准差表示,采用SPSS 22.0统计学软件进行具有一个重复测量的单因素方差分析或t检验,以p<0.05示为具有统计学意义。Experimental data are expressed as mean ± standard deviation. SPSS 22.0 statistical software was used to perform one-way analysis of variance or t test with one repeated measurement. p<0.05 was considered statistically significant.
2.实验结果2.Experimental results
2.1微波辐射对小鼠焦虑情绪行为的影响2.1 Effect of microwave radiation on anxiety behavior in mice
旷场实验结果显示,微波辐射后7d,S波段微波(S-MW)辐射组小鼠中央区域活动时间(图1C)和中央区域活动路程(图1D)均较辐射前显著减少(p<0.05或p<0.01),而且,S-MW组小鼠中央区域活动时间(图1C)较假辐射组(Control)显著减少(p<0.05)。同时,X波段微波(X-MW)辐射组小鼠中央区域活动时间(图1G)和中央区域活动路程(图1H)均较辐射前显著减少(p<0.05或p<0.01)。The results of the open field experiment showed that 7 days after microwave radiation, the central area activity time (Figure 1C) and central area activity distance (Figure 1D) of mice in the S-band microwave (S-MW) radiation group were significantly reduced compared with those before radiation (p<0.05 Or p<0.01), and the central area activity time of mice in the S-MW group (Figure 1C) was significantly reduced compared with the sham radiation group (Control) (p<0.05). At the same time, the central area activity time (Figure 1G) and central area activity distance (Figure 1H) of mice in the X-band microwave (X-MW) radiation group were significantly reduced compared with those before radiation (p<0.05 or p<0.01).
以上表明,S波段和X波段微波辐射均可导致小鼠旷场中央区域活动时间和中央区域活动路程显著减少,提示S波段和X波段微波辐射可引起小鼠焦虑样行为发生,导致情绪行为异常。The above shows that both S-band and .
高架十字迷宫实验结果显示,微波辐射后7d,S-MW组小鼠进入开放臂路程(图2C)较假辐射组(Control)显著减少(p<0.01),而且,S-MW组小鼠进入开放臂时间(图2D)较辐射前显著减少(p<0.05)。同时,X-MW组小鼠进入开放臂路程占比(图2G)和进入开放臂时间占比(图2H)均较辐射前显著减少(p<0.05)。The results of the elevated plus maze experiment showed that 7 days after microwave irradiation, the distance the mice in the S-MW group entered the open arm (Figure 2C) was significantly reduced compared with the sham irradiation group (Control) (p<0.01). Moreover, the mice in the S-MW group entered the open arm. The open arm time (Figure 2D) was significantly reduced compared with before radiation (p<0.05). At the same time, the proportion of mice in the X-MW group entering the open arm (Figure 2G) and the proportion of time entering the open arm (Figure 2H) were significantly reduced compared with those before radiation (p<0.05).
以上表明,S波段和X波段微波辐射均可导致小鼠进入开放臂路程和时间路程显著减少,进一步提示S波段和X波段微波辐射可引起小鼠焦虑样行为发生,导致情绪行为异常。The above shows that both S-band and X-band microwave radiation can cause mice to significantly reduce the distance and time required to enter the open arm, further suggesting that S-band and X-band microwave radiation can cause anxiety-like behavior in mice and lead to abnormal emotional behavior.
2.2微波辐射对小鼠认知行为的影响2.2 Effect of microwave radiation on cognitive behavior of mice
Y迷宫实验结果显示,微波辐射后7d,S-MW组小鼠自由交替率(图3C)较辐射前和假辐射组均显著降低(p<0.05)。同时,X-MW组小鼠自由交替率(图3F)较辐射前显著降低(p<0.05)。The results of the Y maze experiment showed that 7 days after microwave irradiation, the free alternation rate of mice in the S-MW group (Figure 3C) was significantly lower than that of the pre-irradiation and sham irradiation groups (p<0.05). At the same time, the free alternation rate of mice in the X-MW group (Figure 3F) was significantly lower than before radiation (p<0.05).
以上表明,S波段和X波段微波辐射均可导致小鼠自由交替率显著降低,提示S波段和X波段微波辐射可引起小鼠空间探索记忆能力下降。The above shows that both S-band and X-band microwave radiation can significantly reduce the free alternation rate of mice, suggesting that S-band and X-band microwave radiation can cause a decrease in the spatial exploration and memory abilities of mice.
新物体识别实验结果显示,微波辐射后7d,S-MW组小鼠新物体辨别指数(图4C)较辐射前和假辐射组均显著降低(p<0.05)。同时,X-MW组小鼠新物体辨别指数(图4F)较辐射前和假辐射组均显著降低(p<0.01或p<0.05)。The results of the new object recognition experiment showed that 7 days after microwave irradiation, the new object recognition index (Figure 4C) of mice in the S-MW group was significantly lower than that of the pre-irradiation and sham irradiation groups (p<0.05). At the same time, the novel object discrimination index (Figure 4F) of mice in the X-MW group was significantly lower than that of the pre-irradiation and sham-irradiation groups (p<0.01 or p<0.05).
以上表明,S波段和X波段微波辐射均可导致小鼠新物体辨别指数显著降低,提示S波段和X波段微波辐射可引起小鼠事件记忆能力下降,从而导致认知功能障碍。The above shows that both S-band and X-band microwave radiation can cause a significant decrease in the new object discrimination index of mice, suggesting that S-band and X-band microwave radiation can cause a decrease in the event memory ability of mice, leading to cognitive dysfunction.
2.3微波辐射对小鼠血清NSE含量的影响2.3 Effect of microwave radiation on serum NSE content in mice
放射免疫分析结果显示,S-MW和X-MW辐射后6h和7d,辐射组小鼠血清NSE含量均较假辐射组(Control)显著升高(图5A-B,p<0.01或p<0.001),且以X-MW辐射组升高更为显著(图5B,p<0.001),表明S波段和X波段微波辐射均可导致血清NSE含量显著升高。见图5。Radioimmunoassay results showed that at 6h and 7d after S-MW and ), and the increase was more significant in the X-MW radiation group (Figure 5B, p<0.001), indicating that both S-band and X-band microwave radiation can cause a significant increase in serum NSE levels. See Figure 5.
2.4微波辐射对小鼠血清S100β含量的影响2.4 Effect of microwave radiation on serum S100β content in mice
放射免疫分析结果显示,S-MW和X-MW辐射后6h和7d,辐射组小鼠血清S100β含量均较假辐射组(Control)显著升高(图6A-B,p<0.01或p<0.001),且以X-MW辐射组升高更为显著(图6B,p<0.001),表明S波段和X波段微波辐射均可导致血清S100β含量显著升高。见图6。Radioimmunoassay results showed that 6h and 7d after S-MW and ), and the increase was more significant in the X-MW radiation group (Figure 6B, p<0.001), indicating that both S-band and X-band microwave radiation can cause a significant increase in serum S100β content. See Figure 6.
2.5微波辐射对小鼠血清BDNF含量的影响2.5 Effect of microwave radiation on serum BDNF content in mice
放射免疫分析结果显示,S-MW和X-MW辐射后6h和7d,辐射组小鼠血清BDNF含量均较假辐射组(Control)显著降低(图7A-B,p<0.05或p<0.001),且以X-MW辐射组降低更为显著(图7B,p<0.001),表明S波段和X波段微波辐射均可导致血清BDNF含量显著降低。见图7。Radioimmunoassay results showed that 6h and 7d after S-MW and X-MW radiation, the serum BDNF content of mice in the radiation group was significantly lower than that in the sham radiation group (Control) (Figure 7A-B, p<0.05 or p<0.001) , and the decrease was more significant in the X-MW radiation group (Figure 7B, p<0.001), indicating that both S-band and X-band microwave radiation can cause a significant decrease in serum BDNF content. See Figure 7.
2.6微波辐射对小鼠血清VEGF含量的影响2.6 Effect of microwave radiation on serum VEGF content in mice
放射免疫分析结果显示,S-MW辐射后6h,辐射组小鼠血清VEGF含量较假辐射组(Control)显著降低(p<0.05),但辐射后7d变化不明显(p>0.05)。X-MW辐射后6h和7d,辐射组小鼠血清VEGF含量均较Control组均显著降低(图8A-B,p<0.001),且以X-MW辐射组降低更为显著(图8B,p<0.001),表明S波段和X波段微波辐射均可导致血清VEGF含量显著降低。见图8。Radioimmunoassay results showed that 6 hours after S-MW radiation, the serum VEGF content of mice in the radiation group was significantly lower than that in the sham radiation group (Control) (p<0.05), but the change was not obvious 7 days after radiation (p>0.05). 6h and 7d after X-MW radiation, the serum VEGF content of mice in the radiation group was significantly lower than that in the Control group (Figure 8A-B, p<0.001), and the reduction was more significant in the X-MW radiation group (Figure 8B, p <0.001), indicating that both S-band and X-band microwave radiation can cause a significant decrease in serum VEGF content. See Figure 8.
3.讨论3 Discussion
综上所述,我们研究发现,S波段和X波段微波辐射可引起焦虑情绪改变和认知功能损害,中枢神经生化血清学指标NSE、S100β含量显著升高,而血清神经营养因子BDNF、VEGF含量显著下降,表明微波辐射可引起神经细胞受损,参与神经保护的细胞因子BDNF、VEGF减少,细胞膜通透性增加,NSE、S100β释放增多,血脑屏障破坏,血清NSE、S100β含量升高,血清神经营养因子BDNF、VEGF含量降低。另一方面,X-MW较S-MW辐射小鼠血清NSE、S100β、BDNF、VEGF水平变化更为明显。以上提示,电磁辐射所致中枢神经生化血清学指标变化与辐射频率呈正相关,即辐射频率越大,中枢神经生化血清学指标水平变化越大。In summary, our study found that S-band and Significant decrease, indicating that microwave radiation can cause damage to nerve cells, decrease in the cytokines BDNF and VEGF involved in neuroprotection, increase in cell membrane permeability, increase in the release of NSE and S100β, damage to the blood-brain barrier, increase in serum NSE and S100β levels, and serum The levels of neurotrophic factors BDNF and VEGF were reduced. On the other hand, the changes in serum NSE, S100β, BDNF, and VEGF levels in X-MW irradiated mice were more obvious than those in S-MW irradiated mice. The above suggests that changes in central nervous system biochemical serological indicators caused by electromagnetic radiation are positively correlated with radiation frequency, that is, the greater the radiation frequency, the greater the changes in central nervous system biochemical serological indicator levels.
4.结论4 Conclusion
中枢神经生化指标血清NSE、S100β、BDNF、VEGF含量联合应用可作为电磁辐射脑损伤诊断与评价的敏感血清学指标,用于电磁辐射脑损伤相关疾病诊断或动物模型构建。The combined application of serum NSE, S100β, BDNF, and VEGF contents of central nervous system biochemical indicators can be used as sensitive serological indicators for the diagnosis and evaluation of electromagnetic radiation brain injury, and can be used for the diagnosis of electromagnetic radiation brain injury-related diseases or the construction of animal models.
这里说明的模块数量和处理规模是用来简化本发明的说明的。对本发明的应用、修改和变化对本领域的技术人员来说是显而易见的。The number of modules and processing scale described here are intended to simplify the description of the present invention. Applications, modifications and variations of the invention will be apparent to those skilled in the art.
尽管本发明的实施方案已公开如上,但其并不仅仅限于说明书和实施方式中所列运用,它完全可以被适用于各种适合本发明的领域,对于熟悉本领域的人员而言,可容易地实现另外的修改,因此在不背离权利要求及等同范围所限定的一般概念下,本发明并不限于特定的细节和这里示出与描述的图例。Although the embodiments of the present invention have been disclosed above, they are not limited to the applications listed in the description and embodiments. They can be applied to various fields suitable for the present invention. For those familiar with the art, they can easily Additional modifications may be made, and the invention is therefore not limited to the specific details and illustrations shown and described herein without departing from the general concept defined by the claims and equivalent scope.
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