CN109481070B - Implantable internal carotid artery constant-speed injection device and operation method thereof - Google Patents
Implantable internal carotid artery constant-speed injection device and operation method thereof Download PDFInfo
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Abstract
Description
技术领域technical field
本发明涉及小鼠动物模型技术,具体涉及一种植入性颈内动脉恒速注射装置及其操作方法。The invention relates to mouse animal model technology, in particular to an implantable internal carotid artery constant-velocity injection device and an operating method thereof.
背景技术Background technique
在制作各类癌细胞脑转移的小鼠动物模型时,通常需要把小鼠的颈总动脉近心端和颈外动脉结扎,然后使用注射器将体外培养好的癌细胞从颈总动脉远心端进针注射到颈内动脉到达血脑屏障,再自发转移到脑内,制作与人癌症脑转移最为相似的小鼠动物模型。根据局部解剖学可知:颈总动脉向前分为颈外动脉和颈内动脉,只有颈内动脉中的血液流向颅内。因此,唯有将颈外动脉结扎才能使颈总动脉中的血流向前全部流入颈内动脉。由于小鼠手术需要在显微镜下进行,手术操作必须非常精细,手术过程中最关键的步骤是需要结扎小鼠的颈外动脉,然后才能用注射器将癌细胞完全注射到颈内动脉转移至脑,缝扎颈外动脉时必须注意保护伴行的迷走神经和静脉血管不受损伤,否则将会造成小鼠心跳骤停和失血,这是手术失败小鼠死亡的重要原因。另外,结扎颈外动脉成功后,需要将装满癌细胞的注射器的针头刺入颈总动脉远心端(近心端结扎线上方),再向颈内动脉注射体外培养好的癌细胞,注射过程需要严格控制注射速度,即当癌细胞浓度一定的情况下,注射速度越快,单位时间内到达血脑屏障的癌细胞数量就越多,会人为造成癌栓从而堵塞血管,相当于导致小鼠患大面积血栓性疾病而死亡,这也是手术失败小鼠死亡的另一个重要原因。When making mouse animal models of brain metastasis of various cancer cells, it is usually necessary to ligate the proximal end of the common carotid artery and the external carotid artery of the mouse, and then use a syringe to inject cancer cells cultured in vitro from the distal end of the common carotid artery. The needle is injected into the internal carotid artery to reach the blood-brain barrier, and then spontaneously transferred to the brain to create a mouse animal model most similar to human cancer brain metastasis. According to the local anatomy, the common carotid artery is divided forward into the external carotid artery and the internal carotid artery, and only the blood in the internal carotid artery flows into the cranium. Therefore, only by ligation of the external carotid artery can the blood flow in the common carotid artery flow forward into the internal carotid artery. Since mouse surgery needs to be performed under a microscope, the surgical operation must be very delicate. The most critical step in the surgical process is the ligation of the external carotid artery of the mouse, and then the cancer cells can be completely injected into the internal carotid artery and transferred to the brain with a syringe. When suturing the external carotid artery, care must be taken to protect the accompanying vagus nerve and venous vessels from damage, otherwise it will cause cardiac arrest and blood loss in mice, which is an important reason for the death of mice with failed surgery. In addition, after successful ligation of the external carotid artery, the needle of the syringe filled with cancer cells needs to be inserted into the distal end of the common carotid artery (above the ligation line at the proximal end), and then the cancer cells cultivated in vitro are injected into the internal carotid artery. The process needs to strictly control the injection speed, that is, when the concentration of cancer cells is constant, the faster the injection speed, the more cancer cells will reach the blood-brain barrier per unit time, which will artificially cause tumor embolus and block blood vessels, which is equivalent to causing small Mice suffered from extensive thrombotic disease and died, which is another important reason for the death of mice with failed surgery.
发明内容Contents of the invention
针对以上现有技术中存在的问题,本发明提出了一种植入性颈内动脉恒速注射装置及其操作方法,以提高小鼠动物模型制作的成功率,降低小鼠的死亡率。Aiming at the above problems in the prior art, the present invention proposes an implantable constant-velocity injection device for the internal carotid artery and its operation method, so as to improve the success rate of making mouse animal models and reduce the death rate of mice.
本发明的一个目的在于提出一种植入性颈内动脉恒速注射装置。One object of the present invention is to provide an implantable internal carotid artery constant velocity injection device.
本发明的植入性颈内动脉恒速注射装置包括:颈总动脉植入导管、密封盖、密封塞、注射开口、单向流通门、标记物、针头、注射器、推进器、恒速注射微量泵和控制器;其中,颈总动脉植入导管为内部中空的圆筒形的空心导管;颈总动脉植入导管的顶端设置有密封盖,后端设置有密封塞;在颈总动脉植入导管的前端的侧壁上开设有注射开口;在注射开口处且位于颈总动脉植入导管外设置有单向流通门,覆盖注射开口,单向流通门的前端连接在颈总动脉植入导管的前端的侧壁上,单向流通门能够绕着连接处在颈总动脉植入导管外开合;在颈总动脉植入导管的前端设置有标记物;颈总动脉植入导管、密封盖、密封塞、注射开口、单向流通门和标记物构成颈总动脉植入装置;注射器的前端连接针头,针头的形状为具有钝角的折线型;针头穿透密封塞深入至颈总动脉植入导管内;注射器底端的活塞柄连接至推进器;推进器连接至恒速注射微量泵;恒速注射微量泵连接至控制器;注射器的空筒内装有注射物,通过控制器设定注入的速率,控制恒速注射微量泵带动推进器,推动注射器的活塞柄,将注射物通过针头注入颈总动脉植入导管内,通过注射开口,冲开单向流通门流出;注射结束后,由于血液反流的压力强于颈总动脉植入导管内的压力,即颈总动脉植入导管内为负压,单向流通门关闭。The implantable internal carotid artery constant-velocity injection device of the present invention comprises: a common carotid artery implant catheter, a sealing cap, a sealing plug, an injection opening, a one-way flow door, a marker, a needle, a syringe, a pusher, and a constant-velocity injection micro-injection device. Pump and controller; wherein, the common carotid artery implanted catheter is a hollow cylindrical hollow catheter; the top of the common carotid artery implanted catheter is provided with a sealing cover, and the rear end is provided with a sealing plug; An injection opening is opened on the side wall of the front end of the catheter; a one-way flow gate is arranged at the injection opening and outside the common carotid artery implant catheter to cover the injection opening, and the front end of the one-way flow gate is connected to the common carotid artery implant catheter On the side wall of the front end of the common carotid artery implantation catheter, the one-way flow door can be opened and closed around the joint; the front end of the common carotid artery implantation catheter is provided with markers; the common carotid artery implantation catheter, the sealing cap , a sealing plug, an injection opening, a one-way flow gate and markers constitute a common carotid artery implantation device; the front end of the syringe is connected to a needle, and the shape of the needle is a broken line with an obtuse angle; the needle penetrates the sealing plug and is implanted deep into the common carotid artery In the catheter; the piston handle at the bottom of the syringe is connected to the pusher; the pusher is connected to the constant-speed injection micropump; the constant-speed injection micropump is connected to the controller; the empty barrel of the syringe is filled with injection, and the injection rate is set by the controller , control the constant-speed injection micropump to drive the propeller, push the piston handle of the syringe, inject the injection into the common carotid artery implant catheter through the needle, and open the one-way flow door through the injection opening to flow out; after the injection, due to blood backlash The pressure of the flow is stronger than the pressure in the catheter implanted in the common carotid artery, that is, the catheter implanted in the common carotid artery is under negative pressure, and the one-way flow gate is closed.
在进行手术前,将颈总动脉植入导管插入颈总动脉血管中,手术结束后,将颈总动脉植入导管取出。Before the operation, the common carotid artery implant catheter is inserted into the common carotid artery vessel, and the common carotid artery implant catheter is removed after the operation.
颈总动脉植入导管采用聚氯乙烯PVC、聚乙烯PE或聚苯烯PS。颈总动脉植入导管的内径0.5~0.75mm;外径为1~1.25mm。Common carotid artery catheters are made of polyvinyl chloride PVC, polyethylene PE or polystyrene PS. The inner diameter of the catheter implanted in the common carotid artery is 0.5-0.75 mm; the outer diameter is 1-1.25 mm.
密封盖和密封塞的材料采用橡胶、乳胶和硅胶中的一种。The material of the sealing cover and the sealing plug is one of rubber, latex and silica gel.
注射开口的直径为1~2mm,与颈总动脉植入导管顶端的距离为3~4mm。本发明采用密封盖将颈总动脉植入导管的顶端封堵,而在颈总动脉植入导管的侧壁设置注射开口,从而将注射物全部注入至颈内动脉,从而不需要缝扎小鼠的颈外动脉,不会损伤迷走神经和血管。The diameter of the injection opening is 1-2 mm, and the distance from the top of the catheter implanted in the common carotid artery is 3-4 mm. The present invention uses a sealing cap to block the top of the common carotid artery implantation catheter, and sets an injection opening on the side wall of the common carotid artery implantation catheter, so that all the injections are injected into the internal carotid artery, thus eliminating the need for suturing mice The external carotid artery will not damage the vagus nerve and blood vessels.
在注射开口外设置单向流通门,在进行注射过程中,注射物能够冲开单向流通门流出,当注射结束后,由于颈总动脉植入导管内为负压,单向流通门关闭覆盖住注射开口,从而防止颈内动脉里的血液回流至颈总动脉植入导管内。A one-way flow door is set outside the injection opening. During the injection process, the injection can open the one-way flow door and flow out. After the injection is completed, due to the negative pressure in the common carotid artery implant catheter, the one-way flow door is closed and covered. The injection opening is blocked to prevent backflow of blood in the internal carotid artery into the common carotid artery implant catheter.
标记物采用指示条,指示条表面涂有荧光剂;指示条紧粘于密封盖的内表面。The marker is an indicator strip, and the surface of the indicator strip is coated with a fluorescent agent; the indicator strip is tightly adhered to the inner surface of the sealing cover.
针头的钝角为120~145°,不仅便于颈总动脉血管的穿刺操作,更便于植入颈总动脉植入导管,而且进行注射操作时,不会损伤到小鼠的颈总动脉血管。The obtuse angle of the needle is 120-145°, which not only facilitates the puncture operation of the common carotid artery, but also facilitates the implantation of the common carotid artery catheter, and the common carotid artery of the mouse will not be damaged during the injection operation.
注射器包括空筒、活塞和活塞柄;在空筒的顶端设置连通的针头,在活塞的底端设置活塞柄,活塞的前端从空筒的底端深入至空筒内。The syringe includes an empty barrel, a piston and a piston handle; a connected needle is arranged at the top of the empty barrel, a piston handle is arranged at the bottom of the piston, and the front end of the piston goes deep into the empty barrel from the bottom of the empty barrel.
推进器包括推头和丝杠;其中,推头的前端与注射器的活塞柄连接,后端与丝杠连接,丝杠连接至恒速注射微量泵。恒速注射微量泵由控制器控制,控制器的控制信号驱动恒速注射微量泵,带动丝杆旋转,丝杆再带动前端的推头前进,推头能够将丝杆对的旋转运动转变为直线运动,从而推动推头前端的注射器的活塞进行癌细胞或药物注射。The propeller includes a push head and a lead screw; wherein, the front end of the push head is connected to the piston handle of the syringe, the rear end is connected to the lead screw, and the lead screw is connected to a constant-speed injection micropump. The constant-speed injection micropump is controlled by the controller. The control signal of the controller drives the constant-speed injection micropump, which drives the screw to rotate. Movement, thereby pushing the plunger of the syringe at the front end of the push head to inject cancer cells or drugs.
控制器包括电源、输入装置、输出装置和控制电路板;其中,电源分别连接至输入装置、输出装置和控制电路板;控制电路板分别连接至输入装置和输出装置;通过输入装置设定输注速度、注射时间和注射总量,输出装置采用显示屏,显示屏为液晶显示屏LCD。通过设定恒速注射微量泵的输注速度和注射时间进而控制螺杆的旋转速度,达到控制注射器的活塞的前进速度。The controller includes a power supply, an input device, an output device and a control circuit board; wherein the power supply is connected to the input device, the output device and the control circuit board respectively; the control circuit board is respectively connected to the input device and the output device; the infusion is set through the input device Speed, injection time and injection volume, the output device adopts a display screen, and the display screen is a liquid crystal display LCD. By setting the infusion speed and injection time of the constant-speed injection micropump and then controlling the rotation speed of the screw, the forward speed of the plunger of the syringe can be controlled.
注入物的剂量为500~200μl;恒定的注入的速率为0.50~1.0μl/s,注入时间为100~200s。The dose of the injection is 500-200 μl; the constant injection rate is 0.50-1.0 μl/s, and the injection time is 100-200s.
进一步,本发明还包括保护套,保护套套装在颈总动脉植入装置外。Further, the present invention also includes a protective sheath, which is sheathed outside the common carotid artery implantation device.
注射物为向脑部转移的各种癌细胞或者治疗的各种注射药物。The injections are various cancer cells metastasized to the brain or various injected drugs for treatment.
本发明的另一个目的在于提供一种植入性颈内动脉恒速注射装置的操作方法。Another object of the present invention is to provide an operation method of an implantable internal carotid artery constant-velocity injection device.
本发明的植入性颈内动脉恒速注射装置的操作方法,包括以下步骤:The operation method of the implantable internal carotid artery constant velocity injection device of the present invention comprises the following steps:
1)将注射物填充在注射器内;1) Fill the injection in the syringe;
2)将注射器底端的活塞柄连接至推进器;2) Connect the plunger handle at the bottom end of the syringe to the pusher;
3)将推进器连接至恒速注射微量泵;3) Connect the propeller to a constant-speed injection micropump;
4)将恒速注射微量泵连接至控制器;4) Connect the constant-speed injection micropump to the controller;
5)将具有钝角的针头穿透密封塞深入至颈总动脉植入导管内;再穿透密封盖露出针尖;5) The needle with an obtuse angle penetrates the sealing plug deeply into the common carotid artery implant catheter; then penetrates the sealing cover to expose the needle tip;
6)将针尖退回颈总动脉植入导管内;6) Return the needle tip to the common carotid artery implantation catheter;
7)通过控制器设定注入的速率,控制恒速注射微量泵带动推进器,推动注射器的活塞柄,将注射物通过针头注入颈总动脉植入导管内,通过注射开口,冲开单向流通门流出;7) Set the injection rate through the controller, control the constant-speed injection micropump to drive the propeller, push the piston handle of the syringe, inject the injection through the needle into the common carotid artery implant catheter, and open the one-way flow through the injection opening door flow;
8)注射结束后,由于颈总动脉植入导管内为负压,单向流通门关闭。8) After the injection, due to the negative pressure in the common carotid artery implant catheter, the one-way flow door is closed.
本发明的优点:Advantages of the present invention:
本发明采用在颈总动脉植入导管的顶端和后端分别设置即密封又能够被针头刺破的密封盖和密封塞,在颈总动脉植入导管的前端设置由单向流通门覆盖的注射开口,通过控制器控制流速和时间,驱动恒速注射微量泵推动注射器,将癌细胞或注射药物通过颈总动脉植入导管的注射开口流入颈总动脉血管;本发明能够简便手术方法、精简手术步骤,缩短手术时间;同时,将完全改变小鼠颈内动脉注射的动物模型的手术方式,不需要缝扎小鼠的颈外动脉,不会损伤迷走神经和血管,大大提高了手术的成功率。In the present invention, a sealing cover and a sealing plug that are sealed and can be pierced by a needle are respectively arranged at the top and rear ends of the common carotid artery implant catheter, and an injection valve covered by a one-way flow door is arranged at the front end of the common carotid artery implant catheter. Opening, the flow rate and time are controlled by the controller, and the constant-speed injection micropump is driven to push the syringe, so that the cancer cells or injected drugs flow into the common carotid artery through the injection opening of the common carotid artery implant catheter; the invention can simplify and simplify the operation At the same time, it will completely change the surgical method of the mouse internal carotid artery injection animal model, without suturing the external carotid artery of the mouse, and will not damage the vagus nerve and blood vessels, greatly improving the success rate of the operation.
附图说明Description of drawings
图1为本发明的颈总动脉植入装置的一个实施例的示意图;Fig. 1 is the schematic diagram of an embodiment of common carotid artery implantation device of the present invention;
图2为本发明的植入性颈内动脉恒速注射装置的一个实施例的使用前的示意图;Fig. 2 is a schematic diagram before use of an embodiment of the implantable internal carotid artery constant-velocity injection device of the present invention;
图3为本发明的植入性颈内动脉恒速注射装置的一个实施例的使用中的连接示意图。Fig. 3 is a schematic diagram of connection in use of an embodiment of the implantable internal carotid artery constant-velocity injection device of the present invention.
具体实施方式Detailed ways
下面结合附图,通过具体实施例,进一步阐述本发明。The present invention will be further elaborated below through specific embodiments in conjunction with the accompanying drawings.
如图1和2所示,本实施例的植入性颈内动脉恒速注射装置包括:颈总动脉植入导管1、密封盖2、密封塞3、注射开口、单向流通门4、标记物、针头5、注射器6、保护套7、推进器、恒速注射微量泵和控制器;其中,颈总动脉植入导管1为内部中空的圆筒形的空心导管;颈总动脉植入导管1的顶端设置有密封盖2,后端设置有密封塞3;在颈总动脉植入导管1的前端的侧壁上开设有注射开口;在注射开口处且位于颈总动脉植入导管1外设置有单向流通门,覆盖注射开口,单向流通门的前端连接在颈总动脉植入导管1的前端的侧壁上,单向流通门能够绕着连接处在颈总动脉植入导管1外开合;在颈总动脉植入导管1的前端设置有标记物;颈总动脉植入导管1、密封盖2、密封塞3、注射开口、单向流通门4和标记物构成颈总动脉植入装置;保护套7套装在颈总动脉植入装置外;注射器6的前端连接针头5,针头5的形状为具有钝角的折线型;针头5穿透密封塞3深入至颈总动脉植入导管1内;注射器6底端的活塞柄连接至推进器;推进器连接至恒速注射微量泵;恒速注射微量泵连接至控制器;注射器6的空筒内装有注射物,通过控制器设定注入的速率,控制恒速注射微量泵带动推进器,推动注射器6的活塞柄,将注射物通过针头5注入颈总动脉植入导管1内,通过注射开口,冲开单向流通门流出;注射结束后,由于血液反流的压力强于颈总动脉植入导管1内的压力,即颈总动脉植入导管1内为负压,单向流通门关闭。注射器6包括空筒61、活塞62和活塞柄63。As shown in Figures 1 and 2, the implantable internal carotid artery constant-velocity injection device of this embodiment includes: common carotid
在本实施例中,颈总动脉植入导管1采用聚氯乙烯PVC;密封盖2和密封塞3的材料采用橡胶;注射开口的直径为1mm,与颈总动脉植入导管1顶端的距离为3mm。标记物采用指示条,指示条表面涂有荧光剂并紧粘于密封盖2的内表面;针头5的钝角为135°;注入物的剂量为100μl;恒定的注入的速率为0.50μl/s,注入时间在100~200s之间。In the present embodiment, the common carotid
本实施例的植入性颈内动脉恒速注射装置用于小鼠颈内动脉注射的手术中,如图3所示,操作方法包括以下步骤:The implantable internal carotid artery constant-velocity injection device of this embodiment is used in the operation of mouse internal carotid artery injection, as shown in Figure 3, the operation method includes the following steps:
1)将癌细胞或药物填充在注射器6内;1) filling the syringe 6 with cancer cells or medicine;
2)将注射器6底端的活塞柄连接至推进器;2) Connect the piston handle at the bottom end of the syringe 6 to the propeller;
3)将推进器连接至恒速注射微量泵;3) Connect the propeller to a constant-speed injection micropump;
4)将恒速注射微量泵连接至控制器;4) Connect the constant-speed injection micropump to the controller;
5)撕掉保护套7,将颈总动脉植入装置埋入颈总动脉血管管壁,将具有135°钝角的针头5穿透密封塞3深入至颈总动脉植入导管1内;再穿透密封盖2露出针尖;5) Tear off the protective cover 7, embed the common carotid artery implant device into the common carotid artery vessel wall, penetrate the sealing
6)用针尖刺破颈总动脉血管管壁,立即将针尖退回颈总动脉植入导管1内;6) Puncture the vessel wall of the common carotid artery with the needle tip, and immediately return the needle tip to the common carotid
7)通过控制器设定注入的速率,控制恒速注射微量泵带动推进器,推动注射器6的活塞柄,将注射物通过针头5注入颈总动脉植入导管1内,通过注射开口,冲开单向流通门流出;7) Set the injection rate through the controller, control the constant-speed injection micropump to drive the propeller, push the piston handle of the syringe 6, inject the injection into the common carotid
8)注射结束后,由于颈总动脉植入导管1内为负压,单向流通门关闭;8) After the injection, due to the negative pressure in the common carotid
9)手术结束后,将颈总动脉植入装置取出。9) After the operation, the common carotid artery implant device was removed.
最后需要注意的是,公布实施例的目的在于帮助进一步理解本发明,但是本领域的技术人员可以理解:在不脱离本发明及所附的权利要求的精神和范围内,各种替换和修改都是可能的。因此,本发明不应局限于实施例所公开的内容,本发明要求保护的范围以权利要求书界定的范围为准。Finally, it should be noted that the purpose of the disclosed embodiments is to help further understand the present invention, but those skilled in the art can understand that various replacements and modifications can be made without departing from the spirit and scope of the present invention and the appended claims. It is possible. Therefore, the present invention should not be limited to the content disclosed in the embodiments, and the protection scope of the present invention is subject to the scope defined in the claims.
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