CN103519786B - Miniature cerebral apoplexy pathology inducible system for free-motion animal - Google Patents
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Abstract
本发明提供一种用于自由运动动物的微型脑卒中病理诱导系统，包括：支架，所述支架包括一第一光纤束，用于照射一自由运动动物的大脑表面特定位置，诱导该位置的病理变化，其中，所述动物被注射过特定的药物；第二光纤束，用于对所述动物的大脑表面成像范围的照明；成像装置，设置于所述支架的一侧，用于通过所述第二光纤束的照明，捕捉并生成所述第一光纤束照射所述动物大脑表面特定位置时的图像；及底座，设置于所述支架的另一侧，用于将所述支架固定于所述动物的大脑表面；所述支架、成像装置和底座保持同一轴心。
The present invention provides a micro-stroke pathology induction system for freely moving animals, comprising: a bracket, the bracket including a first optical fiber bundle, used to irradiate a specific position on the brain surface of a freely moving animal, and induce pathology at the position Variation, wherein, the animal has been injected with a specific drug; the second optical fiber bundle is used to illuminate the imaging range of the brain surface of the animal; the imaging device is arranged on one side of the bracket for The illumination of the second optical fiber bundle captures and generates an image when the first optical fiber bundle irradiates a specific position on the surface of the animal brain; and the base is arranged on the other side of the bracket for fixing the bracket on the The surface of the brain of the animal; the support, the imaging device and the base keep the same axis.
Description
技术领域 technical field
本发明涉及生物医学技术领域，特别涉及一种用于自由运动动物的微型脑卒中病理诱导系统及方法。 The invention relates to the technical field of biomedicine, in particular to a micro-stroke pathological induction system and method for freely moving animals.
背景技术 Background technique
脑卒中是一种影响脑中动脉系统的疾病。脑卒中发生时，脑中动脉被堵塞或者破裂，血液无法及时向脑组织供应充足的氧气与养料，继而致使脑细胞死亡。脑卒中一直呈高发态势，是导致病人死亡或残疾的主要原因之一。 Stroke is a disease that affects the arterial system in the middle brain. When a stroke occurs, the middle cerebral artery is blocked or ruptured, and the blood cannot supply sufficient oxygen and nutrients to the brain tissue in time, resulting in the death of brain cells. Stroke has always been a high incidence and is one of the main causes of death or disability of patients.
在脑卒中的研究中，动物实验具有重要意义，而在动物体内诱导脑卒中是进行动物实验的前提。目前，动物实验中的脑卒中病理诱导可以较好地模拟人体发病时的病理生理变化情况。但是现阶段的绝大多数研究均是基于已经麻醉的动物进行实验，无法排除麻醉剂对实验的影响。大量的研究报告称，不同的麻醉剂对脑卒中的病理生理变化具有不同的显著影响。例如，麻醉剂对脑卒中的病变组织具有减缓细胞凋亡、缩小病灶体积、避免并发症等保护作用。再如，在麻醉剂作用下，神经系统对躯体刺激的反应也有显著改变。因此，需要提出一种用于清醒动物的脑卒中诱导方法，改善当前的研究。 In the study of stroke, animal experiments are of great significance, and inducing stroke in animals is a prerequisite for animal experiments. At present, the pathological induction of stroke in animal experiments can better simulate the pathophysiological changes of the human body. However, the vast majority of research at this stage is based on experiments on anesthetized animals, and the influence of anesthetics on experiments cannot be ruled out. A large number of studies have reported that different anesthetics have different and significant effects on the pathophysiology of stroke. For example, anesthetics have protective effects such as slowing down apoptosis, reducing the volume of lesions, and avoiding complications in stroke lesion tissues. As another example, under the action of anesthetics, the response of the nervous system to physical stimuli also changes significantly. Therefore, there is a need to propose a stroke induction method for conscious animals that improves the current research.
光化学法是一种具有代表性的微创、快速、精确的脑卒中诱导技术。研究表明，某些光敏物质在特定波长光照的激发下会发生化学变化，变化产物可以进一步与血管壁发生反应从而堵塞血管。光化学法诱导的脑卒中由于光照的位置、范围、能量可控，相比于其他方法，具有精确、稳定的优势。因此光化学法具有广泛的应用。然而，现阶段的光化学法仍无法排除麻醉剂对实验的影响。 Photochemical method is a representative technique for minimally invasive, rapid and precise stroke induction. Studies have shown that some photosensitive substances will undergo chemical changes under the excitation of specific wavelengths of light, and the changed products can further react with blood vessel walls to block blood vessels. Compared with other methods, the stroke induced by photochemical method has the advantages of accuracy and stability due to the controllable position, range and energy of light. Therefore, the photochemical method has a wide range of applications. However, the photochemical method at this stage still cannot rule out the influence of anesthetics on the experiment.
另外，在脑卒中病理的研究过程中，病理过程早期的监测对寻找最佳治疗窗口具有重要意义，因此在临床或实验研究中对病理过程的早期监测至关重要。而光学成像技术作为一种重要的脑成像手段，具有高时空分辨率特性，被 广泛应用于脑科学的研究中。然而，现阶段的实验条件基本不允许同时完成脑卒中的诱导与病理过程的全程实时监测。因此，将脑卒中诱导系统与光学成像系统相互结合，提出一种脑卒中诱导过程中的检测方法尤为重要。 In addition, in the study of stroke pathology, early monitoring of the pathological process is of great significance for finding the best therapeutic window, so early monitoring of the pathological process is very important in clinical or experimental research. As an important brain imaging method, optical imaging technology has the characteristics of high temporal and spatial resolution, and is widely used in the research of brain science. However, the experimental conditions at this stage basically do not allow the induction and pathological process of stroke to be monitored in real time. Therefore, it is particularly important to combine the stroke induction system with the optical imaging system to propose a detection method during the stroke induction process.
发明内容 Contents of the invention
本发明的目的在于提供一种用于自由运动动物的微型脑卒中病理诱导系统及方法，以排除麻醉剂对脑卒中病理诱导的影响，同时实现脑卒中诱导与病理过程的全程实时监测。 The purpose of the present invention is to provide a micro-stroke pathological induction system and method for freely moving animals, so as to eliminate the influence of anesthetics on the pathological induction of stroke, and at the same time realize the whole real-time monitoring of stroke induction and pathological process.
为解决上述技术问题，本发明提供一种用于自由运动动物的微型脑卒中病理诱导系统，包括： In order to solve the above technical problems, the present invention provides a micro-stroke pathological induction system for freely moving animals, including:
支架，所述支架包括一第一光纤束，用于照射一自由运动动物的大脑表面特定位置，诱导该位置的病理变化，其中，所述动物被注射过特定的药物； A stent, the stent comprising a first optical fiber bundle, used to irradiate a specific location on the brain surface of a freely moving animal, and induce pathological changes at the location, wherein the animal has been injected with a specific drug;
第二光纤束，用于对所述动物的大脑表面成像范围的照明； A second fiber optic bundle for illuminating the imaging range of the animal's brain surface;
成像装置，设置于所述支架的一侧，用于通过所述第二光纤束的照明，捕捉并生成所述第一光纤束照射所述动物的大脑表面特定位置时的图像；及 An imaging device, arranged on one side of the bracket, is used to capture and generate an image when the first optical fiber bundle irradiates a specific position on the brain surface of the animal through the illumination of the second optical fiber bundle; and
底座，设置于所述支架的另一侧，用于将所述支架固定于所述动物的大脑表面； a base, arranged on the other side of the bracket, for fixing the bracket to the surface of the brain of the animal;
所述支架、成像装置和底座保持同一轴心。 The support, the imaging device and the base maintain the same axis.
进一步的，在所述的用于自由运动动物的微型脑卒中病理诱导系统中，所述支架还包括金属管，所述第一光纤束传导的光从所述金属管中射出。 Further, in the said micro-stroke pathological induction system for freely moving animals, the bracket further includes a metal tube, and the light guided by the first optical fiber bundle is emitted from the metal tube.
进一步的，在所述的用于自由运动动物的微型脑卒中病理诱导系统中，所述金属管具有调节所述第一光纤束照射在所述动物的大脑表面的角度的功能。 Further, in the micro-stroke pathological induction system for freely moving animals, the metal tube has the function of adjusting the angle at which the first optical fiber bundle is irradiated on the brain surface of the animal.
进一步的，在所述的用于自由运动动物的微型脑卒中病理诱导系统中，所述支架与所述成像装置通过一组弹簧螺丝固定。 Further, in the micro-stroke pathological induction system for freely moving animals, the bracket and the imaging device are fixed by a set of spring screws.
进一步的，在所述的用于自由运动动物的微型脑卒中病理诱导系统中，所述成像装置包括： Further, in the micro-stroke pathological induction system for freely moving animals, the imaging device includes:
镜头，用于捕捉所述第二光纤束照射所述动物的大脑表面特定位置时的图像。 a lens for capturing an image when the second optical fiber bundle irradiates a specific location on the surface of the brain of the animal.
进一步的，在所述的用于自由运动动物的微型脑卒中病理诱导系统中，所 述底座的形状为圆形；所述支架的底部的形状也为圆形。 Further, in the described micro-stroke pathological induction system for freely moving animals, the shape of the base is circular; the shape of the bottom of the bracket is also circular.
同时，本发明还提供一种用于自由运动动物的微型脑卒中病理诱导方法，使用所述的用于自由运动动物的微型脑卒中病理诱导系统，包括： At the same time, the present invention also provides a method for inducing pathological miniature apoplexy in freely moving animals, using the system for inducing pathologically inducing miniature apoplexy in freely moving animals, including:
对动物注射特定的药物； Injecting specific drugs into animals;
第一光纤束照射所述被注射过特定的药物的动物的大脑表面特定位置，诱导该位置的病理变化； The first optical fiber bundle irradiates a specific location on the brain surface of the animal injected with a specific drug, inducing pathological changes at the location;
第二光纤束对所述动物的大脑表面的成像范围照明； a second fiber optic bundle illuminates an imaging field of the animal's brain surface;
成像装置通过所述第二光纤束的照明，捕捉并生成所述第一光纤束照射被注射过特定的药物的动物的大脑表面特定位置时的图像。 The imaging device, through the illumination of the second optical fiber bundle, captures and generates an image when the first optical fiber bundle irradiates a specific position on the brain surface of the animal that has been injected with a specific drug.
进一步的，在所述的用于自由运动动物的微型脑卒中病理诱导方法中，所述支架还包括金属管； Further, in the method for inducing micro-stroke pathology in freely moving animals, the bracket further includes a metal tube;
第一光纤束照射所述被注射过特定的药物的动物的大脑表面特定位置，诱导该位置的病理变化的步骤中，通过调节金属管，使所述第一光纤束传导的光照射在所述动物的大脑表面特定位置，诱导该位置的病理变化。 The first optical fiber bundle irradiates a specific location on the surface of the brain of the animal that has been injected with a specific drug, and in the step of inducing pathological changes at the location, by adjusting the metal tube, the light conducted by the first optical fiber bundle is irradiated on the A specific location on the surface of an animal's brain, inducing pathological changes at that location.
进一步的，在所述的用于自由运动动物的微型脑卒中病理诱导方法中，所述成像装置包括镜头； Further, in the method for inducing micro-stroke pathology in freely moving animals, the imaging device includes a lens;
成像装置通过所述第二光纤束的照明，捕捉并生成所述第一光纤束照射被注射过特定的药物的动物的大脑表面特定位置时的像的步骤中，通过镜头捕捉所述第一光纤束照射被注射过特定的药物的动物的大脑表面特定位置时的图像。 In the step of capturing and generating an image of the first optical fiber bundle irradiating a specific position on the brain surface of an animal that has been injected with a specific drug through the illumination of the second optical fiber bundle, the imaging device captures the image of the first optical fiber bundle through a lens. An image of a beam shining on a specific location on the surface of the brain of an animal that has been injected with a specific drug.
本发明提供的用于自由运动动物的微型脑卒中病理诱导系统及方法，具有以下有益效果：通过金属管中插入的第一光纤束，将传导的光照射在动物的大脑表面特定位置，从而可以引导光化学法需要的特定波长的光线照射动物大脑表面，进行脑卒中的诱导。此外，金属管的角度可以调整，从而使第一光纤束传导的光可以正确地照射动物的大脑表面，在特定位置诱导脑卒中。 The micro-stroke pathological induction system and method for freely moving animals provided by the present invention have the following beneficial effects: through the first optical fiber bundle inserted in the metal tube, the transmitted light is irradiated on a specific position on the surface of the brain of the animal, so that it can Light of a specific wavelength required by the photochemical method is directed to irradiate the surface of the animal's brain to induce stroke. In addition, the angle of the metal tube can be adjusted so that the light conducted by the first fiber optic bundle can correctly illuminate the surface of the animal's brain to induce a stroke at a specific location.
进一步的，在使用第二光纤束传导光线照射动物大脑表面成像范围的情况下，成像装置通过镜头可以实现全程实时成像，第二光纤束传导的光线可以与成像技术相匹配。 Further, in the case of using the second optical fiber bundle to conduct light to irradiate the imaging range of the animal's brain surface, the imaging device can realize full real-time imaging through the lens, and the light conducted by the second optical fiber bundle can match the imaging technology.
附图说明 Description of drawings
图1-2是本发明实施例的用于自由运动动物的微型脑卒中病理诱导系统的结构示意图； Figure 1-2 is a schematic structural view of a micro-stroke pathological induction system for freely moving animals according to an embodiment of the present invention;
图3是本发明实施例的用于自由运动动物的微型脑卒中病理诱导方法的流程图。 Fig. 3 is a flow chart of the pathological induction method for micro-stroke in freely moving animals according to the embodiment of the present invention.
具体实施方式 Detailed ways
以下结合附图和具体实施例对本发明提出的用于自由运动动物的微型脑卒中病理诱导系统及方法作进一步详细说明。根据下面说明和权利要求书，本发明的优点和特征将更清楚。需说明的是，附图均采用非常简化的形式且均使用非精准的比例，仅用以方便、明晰地辅助说明本发明实施例的目的。 The micro-stroke pathological induction system and method for freely moving animals proposed by the present invention will be further described in detail below with reference to the accompanying drawings and specific examples. Advantages and features of the present invention will be apparent from the following description and claims. It should be noted that all the drawings are in a very simplified form and use imprecise scales, and are only used to facilitate and clearly assist the purpose of illustrating the embodiments of the present invention.
如图1和2所示，本发明提供一种用于自由运动动物的微型脑卒中病理诱导系统，应用于动物的大脑表面或身体表面（本实施例具体描述大脑表面），用于动物在自由运动状态下脑卒中病的人工诱导，所述系统包括： As shown in Figures 1 and 2, the present invention provides a micro-stroke pathological induction system for freely moving animals, which is applied to the surface of the brain or body of the animal (this embodiment specifically describes the surface of the brain), and is used for animals in free movement. Artificial induction of stroke under exercise, the system includes:
支架110，所述支架110包括一第一光纤束111，用于照射一动物220的大脑表面特定位置，诱导该特定位置的病理变化，其中，所述动物220被注射过特定的药物； A stent 110, the stent 110 includes a first optical fiber bundle 111, which is used to irradiate a specific position on the brain surface of an animal 220 to induce pathological changes in the specific position, wherein the animal 220 has been injected with a specific drug;
第二光纤束123，用于对所述动物220的大脑表面成像范围的照明； The second optical fiber bundle 123 is used for illuminating the imaging range of the brain surface of the animal 220;
成像装置120，设置于所述支架110的一侧，本实施例为顶部，通过一组弹簧螺丝121与支架110固定，减少了成像装置120的震动。所述成像装置120用于通过所述第二光纤束123的照明，捕捉并生成所述第一光纤束111照射所述动物220的大脑表面特定位置时的图像；及 The imaging device 120 is arranged on one side of the bracket 110 , in this embodiment it is the top, and is fixed to the bracket 110 by a set of spring screws 121 , which reduces the vibration of the imaging device 120 . The imaging device 120 is used to capture and generate an image when the first optical fiber bundle 111 irradiates a specific position on the brain surface of the animal 220 through the illumination of the second optical fiber bundle 123; and
底座210，设置于所述支架110的另一侧，本实施例为底部，用于将所述支架110固定于所述动物220的大脑表面； The base 210 is arranged on the other side of the bracket 110, which is the bottom in this embodiment, and is used to fix the bracket 110 on the surface of the brain of the animal 220;
所述支架110、成像装置120和底座210保持同一轴心。 The support 110 , the imaging device 120 and the base 210 maintain the same axis.
进一步来说，所述支架110还包括金属管112，所述第一光纤束111传导的光从所述金属管112中射出，同时，所述金属管112具有调节所述第一光纤束111照射在所述动物220的大脑表面的角度的功能。也就是说，可以通过调节金属管112的角度，来改变第一光纤束111照射在所述动物220的大脑表面的角度， 能够更准确的使第一光纤束111照射在特定的范围，诱导特定照射范围内的药物与血管壁发生反应从而堵塞血管，诱导脑卒中的病理状态。整个过程没有明显的疼痛反应，符合动物实验的要求。 Further, the bracket 110 also includes a metal tube 112, the light guided by the first optical fiber bundle 111 is emitted from the metal tube 112, and at the same time, the metal tube 112 has the function of adjusting the irradiation of the first optical fiber bundle 111. A function of the angle of the brain surface in the animal 220 . That is to say, the angle at which the first optical fiber bundle 111 is irradiated on the brain surface of the animal 220 can be changed by adjusting the angle of the metal tube 112, so that the first optical fiber bundle 111 can be irradiated in a specific range more accurately and induce a specific range. Drugs in the irradiated range react with the blood vessel wall to block the blood vessel and induce the pathological state of stroke. There was no obvious pain response during the whole process, which met the requirements of animal experiments.
进一步来说，所述成像装置120包括： Further, the imaging device 120 includes:
镜头122，所述第二光纤束123设置于所述镜头122的外圈，所述镜头122用于捕捉所述第二光纤束123照射所述动物220的大脑表面成像范围时的图像； A lens 122, the second optical fiber bundle 123 is arranged on the outer circle of the lens 122, and the lens 122 is used to capture the image when the second optical fiber bundle 123 irradiates the imaging range of the brain surface of the animal 220;
本发明在使用第二光纤束123传导光线照射所述动物220的大脑表面特定成像范围的情况下，成像装置120通过镜头122可以实现全程实时成像，第二光纤束123传导的光线可以与成像技术相匹配。 In the present invention, when the second optical fiber bundle 123 is used to conduct light to irradiate the specific imaging range of the brain surface of the animal 220, the imaging device 120 can realize the whole process of real-time imaging through the lens 122, and the light conducted by the second optical fiber bundle 123 can be compared with the imaging technology. match.
进一步的，在本实施例中，所述底座210的形状为圆形；所述支架110的底部的形状也为圆形。这样支架110和底座210就可以匹配，以固定所述支架110。当所述支架110底部与所述底座210固定为一体后，通过所述第二光纤束123照射动物220的大脑表面的像即可通过所述镜头122被所述成像装置120捕捉。同时，固定在所述支架110的上的第一光纤束111可诱导产生脑卒中病理状态。 Further, in this embodiment, the shape of the base 210 is circular; the shape of the bottom of the support 110 is also circular. In this way, the bracket 110 and the base 210 can be matched to fix the bracket 110 . After the bottom of the bracket 110 is fixed with the base 210 , the image of the brain surface of the animal 220 irradiated by the second optical fiber bundle 123 can be captured by the imaging device 120 through the lens 122 . At the same time, the first optical fiber bundle 111 fixed on the bracket 110 can induce a pathological state of stroke.
本发明用底座210固定于动物220的大脑表面，其他部分通过支架110固定于底座210上，从而在动物220运动过程中，本系统可以与动物220大脑表面保持相对静止状态。 In the present invention, the base 210 is fixed on the surface of the brain of the animal 220, and other parts are fixed on the base 210 through the bracket 110, so that the system can maintain a relatively static state with the brain surface of the animal 220 during the movement of the animal 220.
同时，如图3所示，本发明还提供一种用于自由运动动物的微型脑卒中病理诱导方法，使用所述的用于自由运动动物的微型脑卒中病理诱导系统，包括： Simultaneously, as shown in Figure 3, the present invention also provides a method for inducing pathological miniature apoplexy in freely moving animals, using the pathological inducing system for miniature apoplexy in freely moving animals, including:
S31：对动物注射特定的药物； S31: Inject specific drugs into animals;
S32：第一光纤束照射所述被注射过特定的药物的动物的大脑表面特定位置，诱导该特定位置的病理变化； S32: the first optical fiber bundle irradiates a specific location on the brain surface of the animal injected with a specific drug, and induces pathological changes in the specific location;
具体的，通过调节金属管，从而使所述第一光纤束传导的光照射在所述动物的大脑表面特定位置。 Specifically, by adjusting the metal tube, the light transmitted by the first optical fiber bundle is irradiated on a specific position on the surface of the brain of the animal.
本发明通过金属管中插入的第一光纤束，将传导的光照射在动物的大脑表面，从而可以引导光化学法需要的特定波长的光线照射动物大脑表面，进行脑卒中的诱导。此外，金属管的角度可以调整，从而使第一光纤束引导的光可以正确的照射动物大脑表面，在特定位置诱导脑卒中。 The invention uses the first optical fiber bundle inserted in the metal tube to irradiate the conducted light on the surface of the brain of the animal, thereby guiding light of a specific wavelength required by the photochemical method to irradiate the surface of the animal's brain to induce stroke. In addition, the angle of the metal tube can be adjusted so that the light guided by the first fiber optic bundle can correctly illuminate the surface of the animal's brain to induce a stroke at a specific location.
S33：第二光纤束对所述动物的大脑表面的成像范围照明； S33: the second optical fiber bundle illuminates the imaging range of the animal's brain surface;
S34：成像装置通过所述第二光纤束的照明，捕捉并生成所述第一光纤束照射被注射过特定的药物的动物的大脑表面特定位置时的图像。 S34: The imaging device captures and generates an image when the first optical fiber bundle irradiates a specific position on the brain surface of the animal that has been injected with a specific drug through the illumination of the second optical fiber bundle.
具体的，通过镜头捕捉所述第一光纤束照射被注射过特定的药物的动物的大脑表面时的图像。 Specifically, the lens captures the image when the first optical fiber bundle irradiates the surface of the brain of the animal that has been injected with a specific drug.
在使用第二光纤束传导光线照射动物大脑表面的情况下，成像装置通过镜头可以实现全程实时成像，第二光纤束传导的光线可以与成像技术相匹配。 In the case of using the second optical fiber bundle to conduct light to irradiate the surface of the animal's brain, the imaging device can realize the whole process of real-time imaging through the lens, and the light conducted by the second optical fiber bundle can match the imaging technology.
上述描述仅是对本发明较佳实施例的描述，并非对本发明范围的任何限定，本发明领域的普通技术人员根据上述揭示内容做的任何变更、修饰，均属于权利要求书的保护范围。 The above description is only a description of the preferred embodiments of the present invention, and does not limit the scope of the present invention. Any changes and modifications made by those of ordinary skill in the field of the present invention based on the above disclosures shall fall within the protection scope of the claims.
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