CN107049552B - A kind of experimental provision for manufacturing Chronic Epilepsy animal model - Google Patents
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Abstract
Description
技术领域technical field
本发明属于动物试验技术领域，具体涉及一种用于制造慢性癫痫动物模型的实验装置。The invention belongs to the technical field of animal experiments, and in particular relates to an experimental device for manufacturing chronic epilepsy animal models.
背景技术Background technique
癫痫为最常见的神经系统疾病之一，目前癫痫的定义是反复发作(一般大于三次)的神经元异常放电引起的暂时性的中枢神经系统功能失常，其神经外科具有器质性的损害。癫痫的患病率为0.5--0.7％，全球约有3500万病例，我国约650万患者正在遭受它的困扰。癫痫的反复发作可造成海马等重要结构的神经元选择性死亡，造成患者记忆，认知和情感等多方面功能的障碍。Epilepsy is one of the most common nervous system diseases. Currently, epilepsy is defined as temporary central nervous system dysfunction caused by recurrent (generally more than three) abnormal discharge of neurons, and its neurosurgery has organic damage. The prevalence of epilepsy is 0.5--0.7%. There are about 35 million cases in the world, and about 6.5 million patients in my country are suffering from it. Recurrent epilepsy can cause the selective death of neurons in important structures such as the hippocampus, resulting in impairments in memory, cognition, and emotion.
近年来，对于癫痫的手术及药物治疗虽然取得了一些进展，但仍有约30％的癫痛病人难于完全控制发作，而且即使是那些可以通过药物完全控制发作的癫痫病人也往往需要长期服药，给癫痛病人及社会均带来了很大的负担。In recent years, although some progress has been made in the operation and drug treatment of epilepsy, about 30% of epilepsy patients are still difficult to completely control their seizures, and even those epilepsy patients who can completely control their seizures through drugs often need long-term medication. All brought very big burden to epilepsy patient and society.
建立符合癫痫疾病情况的动物模型将大大有助于对于此特定疾病的病理生理过程的深入理解，从而可以进一步的研究治疗方法。如今，有制造“惊厥”的各种动物模型和制造“癫痫”的各种动物模型两种类型；用于癫痫研究的动物模型则包括戊四氮等注射方法的12种模型，理想的癫痫模型必须痫性活动易诱发，且保留时间较长，是一种慢性模型。The establishment of animal models consistent with epilepsy will greatly contribute to the in-depth understanding of the pathophysiological process of this specific disease, so that further research on treatment methods can be carried out. Today, there are two types of animal models that produce "convulsions" and various animal models that produce "epilepsy"; animal models for epilepsy research include 12 models of injection methods such as pentylenetetrazol, the ideal epilepsy model Must be easy to induce epileptic activity, and longer retention time, is a chronic model.
脑卒中分为脑出血和脑缺血，而大约80-85％的卒中为缺血性脑卒中；而在缺血性脑卒中，又可以进一步的分为局灶性脑缺血及全脑缺血，而后者则多发生于心脏骤停、溺水、休克低血压及动脉瘤性蛛网膜下腔出血伴发全脑血管痉挛等情况下，其癫痫的发生率更高，治疗难度更大，效果更差。Stroke is divided into cerebral hemorrhage and cerebral ischemia, and about 80-85% of strokes are ischemic strokes; and in ischemic strokes, it can be further divided into focal cerebral ischemia and global cerebral ischemia. Blood, while the latter mostly occurs in cardiac arrest, drowning, shock hypotension and aneurysmal subarachnoid hemorrhage accompanied by global cerebral vasospasm, etc., the incidence of epilepsy is higher, the treatment is more difficult, and the effect worse.
现有技术中，进行的实验研究只是在研究癫痫(抽搐)的早期情况，未能研究其持续状态。所以，该动物模型严格地说只是惊厥的大鼠模型(一次性的或偶然的，未造成永久的严重的脑损害)，而非癫痫的动物模型。其神经病理改变也往往是抽搐或缺血发作的结果，而非是癫痫的原因。国外，美国肯塔基大学的Reid教授的实验室建立了声音诱发的Wistar大鼠脑缺血抽搐模型，其发作形式也是惊厥模式，为短时程的癫痫性发作。在我们的实验中，观察到少数一些严重的全脑缺血的大鼠可表现为慢性的癫痫状态，脑电图亦有明确的长时程改变。In the prior art, the experimental research carried out is only to study the early stage of epilepsy (convulsions), but fails to study its continuous state. Therefore, strictly speaking, this animal model is only a rat model of convulsions (one-time or accidental, without causing permanent serious brain damage), not an animal model of epilepsy. The neuropathological changes are also often the result of convulsions or ischemic attacks rather than the cause of epilepsy. Abroad, the laboratory of Professor Reid of the University of Kentucky in the United States has established a sound-induced cerebral ischemic convulsion model in Wistar rats, and its seizure form is also a convulsion mode, which is a short-term epileptic seizure. In our experiments, it was observed that a small number of rats with severe global cerebral ischemia could manifest chronic epileptic status, and there were also clear long-term changes in EEG.
癫痫是全脑缺血达到″一定程度″的结果，这″一定程度″与全脑缺血的程度和时间有关。如果″一定程度″时间短，大鼠脑损伤不严重，癫痫不发生或发生率非常低；如果″一定程度″时间长，则大鼠的脑、心、肺、肾等损伤严重，动物死亡率极高。Epilepsy is the result of global cerebral ischemia reaching a "certain degree", which is related to the degree and time of global cerebral ischemia. If the "certain degree" time is short, the brain injury of the rat is not serious, and the epilepsy does not occur or the incidence rate is very low; if the "certain degree" time is long, the brain, heart, lung, kidney, etc. of the rat are severely damaged, and the animal mortality rate extremely high.
为了研究癫痫的原理和治疗方案，专利CN201120062009.7提出一种对动物胸部进行压迫的胸部压迫仪，但是此设备较为简单，癫痫的诱因有很多，单纯的进行胸部压迫来达到制造动物癫痫的效果的成功率较低，因此需要一种能够提供多种癫痫发病诱因同时还可实时监控动物的生理参数装置，以此提高实验的成功率。In order to study the principle and treatment plan of epilepsy, the patent CN201120062009.7 proposes a chest compression instrument for compressing the chest of animals, but this device is relatively simple, and there are many causes of epilepsy. Simply perform chest compression to achieve the effect of producing animal epilepsy The success rate of the experiment is low, so there is a need for a device that can provide multiple epilepsy triggers and monitor the animal's physiological parameters in real time, so as to improve the success rate of the experiment.
发明内容Contents of the invention
针对以上技术问题，本发明提供一种用于制造慢性癫痫动物模型的实验装置，包含多种癫痫发病的诱因，实验成功率高。Aiming at the above technical problems, the present invention provides an experimental device for producing animal models of chronic epilepsy, which contains multiple causes of epilepsy and has a high success rate of the experiment.
本发明的技术方案为：一种用于制造慢性癫痫动物模型的实验装置，主要包括实验箱、活动托板、控制室、配电室和升降压迫装置，所述实验箱分为上室和下室，所述上室的体积为下室的二分之一，实验箱下室的底板中心位置上设有LED灯盘，实验箱下室的后侧壁的左上方设有进气孔，所述进气孔通过导气管连接有储气罐，所述储气罐上设有电磁比例阀门，实验箱下室的左侧壁上设有制冷通孔，所述制冷通孔通过冷气管连接有制冷机，实验箱下室的后侧壁的右上方设有出气孔，实验箱下室的右侧壁上方设有音频发生器，实验箱上室的上方设有推拉盖板，所述活动托板通过转轴连接在实验箱上室和下室交界处的横轴中心位置，活动托板的中心位置设有限位固定装置，限位固定装置的右侧设有脑电波监测装置，脑电波监测装置的左侧设有温度传感器，脑电波监测装置的右侧设有氧浓度检测传感器，所述控制室位于实验箱的右侧，控制室为直角梯形体，控制室内部设有集成控制器，所述集成控制器的左边设有电机，所述电机的上方连接有连轴器，所述连轴器的上方连接有拐角减速器，所述拐角减速器与所述转轴的左端相连，转轴与拐角减速器之间设有锁定构件，控制室的上顶面上设有控制面板，所述配电室连接在控制室的底部，所述升降压迫装置连接在实验箱后侧壁的中心位置，升降压压迫装置包括升降驱动器、升降支撑杆、L型连接杆和压板，所述升降支撑杆连接在所述升降驱动器的上方中心位置，所述L型连接杆的水平段固定连接在升降支撑杆的侧面，所述压板固定连接在L型连接杆的竖直段的末端，升降支撑杆顶端活动连接有横杆，所述横杆的末端下方设有加热灯。The technical solution of the present invention is: an experimental device for manufacturing animal models of chronic epilepsy, which mainly includes an experimental box, a movable pallet, a control room, a power distribution room and a lifting compression device. The experimental box is divided into an upper room and a lower room. The volume of the upper chamber is one-half of the lower chamber, the center of the bottom plate of the lower chamber of the experimental box is provided with an LED lamp panel, and the upper left side of the rear side wall of the lower chamber of the experimental box is provided with an air inlet. The air intake hole is connected to an air storage tank through an air guide pipe, and an electromagnetic proportional valve is provided on the air storage tank. A cooling through hole is provided on the left side wall of the lower chamber of the experiment box, and the cooling through hole is connected to a Refrigerator, an air outlet is provided on the upper right side of the rear side wall of the lower room of the test box, an audio generator is provided above the right side wall of the lower room of the test box, a push-pull cover plate is provided above the upper room of the test box, and the movable support The plate is connected to the center of the horizontal axis at the junction of the upper chamber and the lower chamber of the experimental box through a rotating shaft. The center of the movable pallet is provided with a limit fixing device, and the right side of the limit fixing device is equipped with a brain wave monitoring device. There is a temperature sensor on the left side of the brainwave monitoring device, and an oxygen concentration detection sensor on the right side of the brain wave monitoring device. The control room is located on the right side of the experiment box. A motor is provided on the left side of the integrated controller, a shaft coupling is connected above the motor, a corner reducer is connected above the shaft coupling, the corner reducer is connected with the left end of the rotating shaft, and the rotating shaft and the corner A locking member is provided between the reducers, a control panel is provided on the upper top surface of the control room, the power distribution room is connected to the bottom of the control room, and the lifting and pressing device is connected to the center of the rear side wall of the test box. The depressurization compression device includes a lifting driver, a lifting support rod, an L-shaped connecting rod and a pressing plate, the lifting supporting rod is connected at the upper center of the lifting driver, and the horizontal section of the L-shaped connecting rod is fixedly connected to the lifting supporting rod The side of the side, the pressure plate is fixedly connected to the end of the vertical section of the L-shaped connecting rod, the top of the lifting support rod is movably connected to a cross bar, and a heating lamp is arranged below the end of the cross bar.
进一步的，所述储气罐内部为二氧化碳气体或空气与二氧化碳的混合气体，所述空气与二氧化碳的气体体积比为5-10:1，利用二氧化碳气体使得实验箱氧浓度降低，达到实验鼠脑部缺氧的症状，依次诱发癫痫发生。Further, the interior of the gas storage tank is carbon dioxide gas or a mixed gas of air and carbon dioxide, the gas volume ratio of the air and carbon dioxide is 5-10:1, and the oxygen concentration of the experimental box is reduced by using carbon dioxide gas, reaching the level of the brain of the experimental rat. Symptoms of hypoxia in the brain, which in turn induce epilepsy.
进一步的，所述实验装置的癫痫诱发模式包括胸外压迫刺激、环境缺氧刺激、温度刺激、光线刺激和眩晕刺激五种模式，上述五种刺激可单独实施或任意几种组合实施，组合式癫痫诱发装置刺激方式齐全，能大大提高实验的成功率。Further, the epilepsy-inducing mode of the experimental device includes five modes of external chest compression stimulation, environmental hypoxia stimulation, temperature stimulation, light stimulation and vertigo stimulation. The above five stimulations can be implemented alone or in any combination. The epilepsy-inducing device has complete stimulation methods, which can greatly improve the success rate of the experiment.
进一步的，所述脑电波监测装置主要包括半球形脑电波监测器、导轨条、挡板和压缩弹簧，所述导轨条固定连接在所述活动托板的上表面并关于活动托板的横轴中心左右对称，所述挡板的底面固定连接在活动托板的上表面，挡板的左侧面与导轨条的右端面固定连接，所述半球形脑电波监测器通过滑槽块与导轨条活动连接，所述压缩弹簧连接在半球形脑电波监测器与挡板之间，通过压缩弹簧连接半球形脑电波监测器，可使得半球形脑电波监测器根据实验鼠的大小弹性调节其与头部的距离，贴合度高，测量结果精确。Further, the brainwave monitoring device mainly includes a hemispherical brainwave monitor, a guide rail, a baffle and a compression spring, and the guide rail is fixedly connected to the upper surface of the movable pallet and is about the horizontal axis of the movable pallet. The left and right sides of the center are symmetrical, the bottom surface of the baffle is fixedly connected to the upper surface of the movable supporting plate, the left side of the baffle is fixedly connected to the right end surface of the guide rail, and the hemispherical brain wave monitor passes through the chute block and the guide rail. Movably connected, the compression spring is connected between the hemispherical brain wave monitor and the baffle, and the hemispherical brain wave monitor is connected through the compression spring, so that the hemispherical brain wave monitor can be elastically adjusted to the head according to the size of the experimental mouse. The distance between the parts, the fit is high, and the measurement results are accurate.
进一步的，所述限位固定装置包括压力传感器、左支座、左弧块、右支座、右弧块、第一松紧带和第二松紧带，所述压力传感器内嵌于所述活动托板的中心位置，所述左支座和右支座分别固定连接在压力传感器的左右两侧，所述左弧块和右弧块分别滑动连接在左支座和右支座上，所述第一松紧带的一端固定连接在左支座的前方，所述第二松紧带的一端固定连接在左支座的后方,所述右支座的后方设有第一卡槽，右支座的前方设有第二卡槽，通过松紧带弹性固定实验鼠，可预留活动空间，尤其在胸外压迫刺激时可降低实验鼠的死亡率。Further, the limit fixing device includes a pressure sensor, a left support, a left arc block, a right support, a right arc block, a first elastic band and a second elastic band, and the pressure sensor is embedded in the movable pallet center position, the left support and the right support are respectively fixedly connected to the left and right sides of the pressure sensor, the left arc block and the right arc block are respectively slidably connected to the left support and the right support, and the first elastic band One end of the second elastic band is fixedly connected to the front of the left support, one end of the second elastic band is fixedly connected to the rear of the left support, the rear of the right support is provided with a first card slot, and the front of the right support is provided with a second The card slot is used to elastically fix the experimental mice with elastic bands, which can reserve space for activities, and can especially reduce the death rate of experimental mice when the chest is compressed and stimulated.
进一步的，所述加热灯的上方设有聚光罩，加热灯为白炽灯或迷你陶瓷加热灯的其中一种，数量为1-3个，通过加热灯和聚光罩对实验鼠进行温度刺激中的热刺激。Further, a spotlight is provided above the heating lamp, and the heating lamp is one of incandescent lamps or mini ceramic heating lamps, the number is 1-3, and the temperature stimulation is performed on the experimental mice through the heating lamp and the spotlight. thermal stimulus in .
进一步的，所述控制面板包括显示屏、操作按钮板、一号连接孔和二号连接孔，所述显示屏位于操作面板的上方，所述操作按钮板位于显示屏的左下方，所述一号连接孔和二号连接孔分别位于显示屏的右下方，一号连接孔和二号连接孔分别通过导线一和导线二与所述电磁比例阀门和制冷机相连，通过一号连接孔和二号连接孔外接的储气罐和制冷机，以此实现集中控制。Further, the control panel includes a display screen, an operation button board, a No. 1 connection hole and a No. 2 connection hole, the display screen is located above the operation panel, the operation button board is located at the lower left of the display screen, and the first The No. 1 connection hole and the No. 2 connection hole are respectively located at the lower right of the display screen. The No. 1 connection hole and the No. 2 connection hole are respectively connected to the electromagnetic proportional valve and the refrigerator through the wire 1 and the wire 2. The air storage tank and the refrigerator connected to the No. connection hole, so as to realize centralized control.
本发明的工作方法为：先打开所述推拉盖板，将实验鼠放置在所述限位固定装置的中心位置，利用所述左弧块和右弧块初步固定，再利用所述第一松紧带和第二松紧带交叉固定，然后将实验鼠的头部放置到所述半球形脑电波监测器内，选择刺激模式；当选择胸外压迫刺激时，通过所述升降驱动器调节所述升降支撑杆的高度，使得所述压板与实验鼠胸部贴合，并进行一定力度的按压，按压过程中关注所述显示屏中的脑电波信号，以此监测实验鼠的生理状况；当选择环境缺氧刺激时，将活动托板通过所述电机、连轴器和拐角减速器的作用翻转度，盖上推拉盖板，利用储气罐向所述实验箱内充入一定比例的二氧化碳气体或二氧化碳与空气的混合气体，并利用所述氧浓度检测传感器和半球形脑电波监测器的反应情况联动调节实验箱的缺氧度；当选择温度刺激模式时，先利用所述加热灯和聚光罩对实验鼠进行热刺激，然后将活动托板翻转度，利用所述制冷机对实验鼠进行冷刺激，如此循环往复，并利用所述温度传感器和半球形脑电波监测器的反应情况联动调节实验箱的温度；当选择光线刺激模式时，将活动托板翻转度，使实验鼠对准所述LED灯盘，利用光线的明暗闪烁变化对实验鼠进行光线刺激，并利用半球形脑电波监测器监测实验鼠的反应情况；当选择眩晕刺激模式时，利用电机、连轴器和拐角减速器将固定在活动托板上的实验鼠进行恒速或变速的上下翻转，并利用半球形脑电波监测器监测实验鼠的反应情况。The working method of the present invention is as follows: firstly open the push-pull cover plate, place the experimental mouse at the center of the limit fixing device, use the left arc block and the right arc block to initially fix it, and then use the first elastic band Cross and fix the second elastic band, then place the head of the experimental mouse in the hemispherical EEG monitor, and select the stimulation mode; Height, so that the pressure plate fits the chest of the experimental mouse, and presses with a certain strength, and pays attention to the brain wave signal in the display screen during the pressing process, so as to monitor the physiological condition of the experimental mouse; when the environmental hypoxia stimulation is selected , turn the movable pallet through the action of the motor, coupling and corner reducer, cover the push-pull cover, and use the gas storage tank to fill the test box with a certain proportion of carbon dioxide gas or a mixture of carbon dioxide and air. Mix the gas, and use the reaction situation of the oxygen concentration detection sensor and the hemispherical brain wave monitor to adjust the degree of hypoxia in the experimental box; Perform thermal stimulation, then flip the movable pallet to a certain degree, use the refrigerator to perform cold stimulation on the experimental mice, repeat this cycle, and use the temperature sensor and the response of the hemispherical brain wave monitor to adjust the temperature of the experimental box in linkage ; When the light stimulation mode is selected, the movable support plate is turned over, so that the experimental mice are aligned with the LED lamp panel, and the experimental mice are stimulated with light by using the light and dark flickering changes of the light, and the experimental mice are monitored by a hemispherical brain wave monitor. When the vertigo stimulation mode is selected, use the motor, coupling and corner reducer to turn the experimental mouse fixed on the movable pallet up and down at a constant or variable speed, and use a hemispherical brain wave monitor to monitor the experimental rats. The reaction of the mouse.
与现有技术相比，本发明的有益效果为：本发明的用于制造慢性癫痫动物模型的实验装置本发明利用活动托板将实验箱分为两部分，使其能够进行多种诱发模式，可以前期用来制造癫痫病症，也可后期用来刺激诱发癫痫病症，其中利用Compared with the prior art, the beneficial effects of the present invention are: the present invention is used to manufacture the experimental device of the chronic epilepsy animal model. The present invention utilizes the movable pallet to divide the experimental box into two parts, so that it can carry out multiple induction modes, It can be used to create epilepsy in the early stage, and it can also be used to stimulate and induce epilepsy in the later stage.
升降压迫装置对实验鼠的胸部进行按压以此到达实验鼠的大脑缺氧和缺血，利用二氧化碳制造缺氧环境，以此达到实验鼠脑部缺氧；利用加热灯和制冷机对实验鼠进行冷热交替的温度变化刺激；利用LED灯盘对实验鼠进行光线刺激；利用电机、连轴器和拐角减速器将固定在活动托板上的实验鼠进行恒速或变速的上下翻转，实现眩晕刺激；同时利用压力传感器、温度传感器、氧浓度检测传感器及半球形脑电波监测器对实验箱环境及实验鼠的生理状况进行实施监控和调节。总之，本发明设计合理，空间利用率高，功能齐全，大大的降低了实验鼠的死亡率并提高了试验的成功率。The lifting compression device presses the chest of the experimental mice to reach the brain hypoxia and ischemia of the experimental mice, and uses carbon dioxide to create an anoxic environment to achieve brain hypoxia of the experimental mice; uses the heating lamp and refrigerator to treat the experimental mice. Alternate cold and hot temperature change stimulation; LED light panel is used to stimulate the experimental mice with light; the experimental mice fixed on the movable pallet are turned up and down at a constant or variable speed by using the motor, coupling and corner reducer to achieve vertigo Stimulation; at the same time, the pressure sensor, temperature sensor, oxygen concentration detection sensor and hemispherical brain wave monitor are used to monitor and adjust the experimental box environment and the physiological conditions of the experimental mice. In a word, the present invention has reasonable design, high space utilization rate and complete functions, which greatly reduces the death rate of experimental rats and improves the success rate of experiments.
附图说明Description of drawings
图1是本发明的整体结构示意图；Fig. 1 is the overall structural representation of the present invention;
图2是本发明的后视结构示意图；Fig. 2 is the rear view structure schematic diagram of the present invention;
图3是本发明的活动托板的俯视图；Fig. 3 is the top view of movable pallet of the present invention;
图4是本发明的活动托板的左视图；Fig. 4 is the left side view of movable pallet of the present invention;
图5是本发明的活动托板的制动连接关系示意图；Fig. 5 is a schematic diagram of the brake connection relationship of the movable pallet of the present invention;
图6是本发明的半球形脑电波监测器的剖视图；Fig. 6 is a sectional view of the hemispherical EEG monitor of the present invention;
图7是本发明的控制面板的示意图。Fig. 7 is a schematic diagram of the control panel of the present invention.
其中，1-实验箱、2-活动托板、3-控制室、4-配电室、5-升降压迫装置、51-升降驱动器、52-升降支撑杆、53-L型连接杆、54-压板、55-横杆、56-加热灯、57-聚光罩、6-LED灯盘、7-进气孔、8-导气管、9-储气罐、10-电磁比例阀门、11-制冷通孔、12-冷气管、13-制冷机、14-出气孔、15-音频发生器、16-推拉盖板、17-转轴、18-限位固定装置、180-压力传感器、181-左支座、182-左弧块、183-右支座、184-右弧块、185-第一松紧带、186-第二松紧带、187-第一卡槽、188-第二卡槽、19-脑电波监测装置、190-半球形脑电波监测器、191-导轨条、192-挡板、193-压缩弹簧、194-滑槽块、20-温度传感器、21-氧浓度检测传感器、22-集成控制器、23-电机、24-连轴器、25-拐角减速器、26-锁定构件、27-控制面板、270-显示屏、271-操作按钮板、272-一号连接孔、273-二号连接孔、100-导线一、130-导线二。Among them, 1-experiment box, 2-movable pallet, 3-control room, 4-power distribution room, 5-lifting compression device, 51-lifting driver, 52-lifting support rod, 53-L-shaped connecting rod, 54- Pressing plate, 55-horizontal bar, 56-heating lamp, 57-concentrator, 6-LED lamp panel, 7-intake hole, 8-air duct, 9-air storage tank, 10-electromagnetic proportional valve, 11-refrigeration Through hole, 12-air-cooling pipe, 13-refrigerator, 14-air outlet, 15-audio generator, 16-push-pull cover, 17-rotating shaft, 18-limit fixing device, 180-pressure sensor, 181-left branch Seat, 182-left arc block, 183-right support, 184-right arc block, 185-first elastic band, 186-second elastic band, 187-first card slot, 188-second card slot, 19-brain wave Monitoring device, 190-hemispherical brain wave monitor, 191-rail rail, 192-baffle plate, 193-compression spring, 194-chute block, 20-temperature sensor, 21-oxygen concentration detection sensor, 22-integrated controller , 23-motor, 24-coupling, 25-corner reducer, 26-locking member, 27-control panel, 270-display screen, 271-operation button board, 272-connection hole No. 1, 273-connection No. 2 Holes, 100-wire one, 130-wire two.
具体实施方式Detailed ways
为便于对本发明实施例的理解，下面以具体实施例为例做进一步的解释说明，实施例并不构成对本发明实施例的限定。In order to facilitate the understanding of the embodiments of the present invention, specific embodiments are taken as examples below for further explanation, and the embodiments do not constitute limitations on the embodiments of the present invention.
如图1所示，一种用于制造慢性癫痫动物模型的实验装置，其中，癫痫诱发模式包括胸外压迫刺激、环境缺氧刺激、温度刺激、光线刺激和眩晕刺激五种模式，上述五种刺激可单独实施或任意几种组合实施，组合式癫痫诱发装置刺激方式齐全，能大大提高实验的成功率。主要包括实验箱1、活动托板2、控制室3、配电室4和升降压迫装置5，实验箱1分为上室和下室，上室的体积为下室的二分之一，实验箱1下室的底板中心位置上设有LED灯盘6，实验箱1下室的后侧壁的左上方设有进气孔7，进气孔7通过导气管8连接有储气罐9，其中，储气罐9内部为空气与二氧化碳的混合气体，空气与二氧化碳的气体体积比为8:1，利用二氧化碳气体使得实验箱氧浓度降低，达到实验鼠脑部缺氧的症状，依次诱发癫痫发生。储气罐9上设有电磁比例阀门10，实验箱1下室的左侧壁上设有制冷通孔11，制冷通孔11通过冷气管12连接有制冷机13，实验箱1下室的后侧壁的右上方设有出气孔14，实验箱1下室的右侧壁上方设有音频发生器15，实验箱1上室的上方设有推拉盖板16，活动托板2通过转轴17连接在实验箱1上室和下室交界处的横轴中心位置，活动托板2的中心位置设有限位固定装置18，如图3、4所示，限位固定装置18包括压力传感器180、左支座181、左弧块182、右支座183、右弧块184、第一松紧带185和第二松紧带186，压力传感器180内嵌于活动托板2的中心位置，左支座181和右支座183分别固定连接在压力传感器180的左右两侧，左弧块182和右弧块184分别滑动连接在左支座181和右支座183上，第一松紧带185的一端固定连接在左支座181的前方，第二松紧带186的一端固定连接在左支座181的后方,右支座的后方设有第一卡槽187，右支座的前方设有第二卡槽188，通过松紧带弹性固定实验鼠，可预留活动空间，尤其在胸外压迫刺激时可降低实验鼠的死亡率。限位固定装置18的右侧设有脑电波监测装置19，如图3、4、6所示，脑电波监测装置19主要包括半球形脑电波监测器190、导轨条191、挡板192和压缩弹簧193，导轨条191固定连接在活动托板2的上表面并关于活动托板2的横轴中心左右对称，挡板192的底面固定连接在活动托板2的上表面，挡板192的左侧面与导轨条191的右端面固定连接，半球形脑电波监测器190通过滑槽块194与导轨条191活动连接，压缩弹簧193连接在半球形脑电波监测器190与挡板192之间，通过压缩弹簧193连接半球形脑电波监测器190，可使得半球形脑电波监测器190根据实验鼠的大小弹性调节其与头部的距离，贴合度高，测量结果精确。脑电波监测装置19的左侧设有温度传感器20，脑电波监测装置19的右侧设有氧浓度检测传感器21，控制室3位于实验箱1的右侧，控制室3为直角梯形体，控制室3内部设有集成控制器22，集成控制器22的左边设有电机23，电机23的上方连接有连轴器24，连轴器24的上方连接有拐角减速器25，拐角减速器25与转轴17的左端相连，转轴17与拐角减速器25之间设有锁定构件26，控制室3的上顶面上设有控制面板27，如图1、7所示，控制面板27包括显示屏270、操作按钮板271、一号连接孔272和二号连接孔273，显示屏270位于操作面板27的上方，操作按钮板271位于显示屏27的左下方，一号连接孔272和二号连接孔273分别位于显示屏27的右下方，一号连接孔272和二号连接孔273分别通过导线一100和导线二130与电磁比例阀门10和制冷机13相连，通过一号连接孔272和二号连接孔273外接的储气罐和制冷机，以此实现集中控制。配电室4连接在控制室3的底部，升降压迫装置5连接在实验箱1后侧壁的中心位置，升降压压迫装置5包括升降驱动器51、升降支撑杆52、L型连接杆53和压板54，升降支撑杆52连接在升降驱动器51的上方中心位置，L型连接杆53的水平段固定连接在升降支撑杆52的侧面，压板54固定连接在L型连接杆53的竖直段的末端，升降支撑杆52顶端活动连接有横杆54，横杆55的末端下方设有加热灯56。如图1、2所示，加热灯56的上方设有聚光罩57，加热灯为白炽灯或迷你陶瓷加热灯的其中一种，数量为1个，通过加热灯和聚光罩对实验鼠进行温度刺激中的热刺激。As shown in Figure 1, an experimental device for making animal models of chronic epilepsy, wherein the epilepsy-inducing modes include five modes of external chest compression stimulation, environmental hypoxia stimulation, temperature stimulation, light stimulation and vertigo stimulation, the above five Stimulation can be implemented alone or in any combination. The combined epilepsy inducing device has complete stimulation methods, which can greatly improve the success rate of the experiment. It mainly includes a test box 1, a movable pallet 2, a control room 3, a power distribution room 4 and a lifting and pressing device 5. The test box 1 is divided into an upper room and a lower room, and the volume of the upper room is half of the lower room. An LED lamp panel 6 is arranged on the center of the bottom plate of the lower chamber of the box 1, and an air inlet 7 is arranged on the upper left side of the rear side wall of the lower chamber of the experimental box 1, and the air inlet 7 is connected to an air storage tank 9 through an air guide pipe 8. Among them, the inside of the gas storage tank 9 is a mixed gas of air and carbon dioxide, and the gas volume ratio of air and carbon dioxide is 8:1. The oxygen concentration of the experimental box is reduced by using carbon dioxide gas, so as to achieve the symptoms of brain hypoxia in experimental mice and induce epilepsy in turn. occur. The air storage tank 9 is provided with an electromagnetic proportional valve 10, and the left side wall of the lower chamber of the experimental box 1 is provided with a cooling through hole 11, which is connected to a refrigerator 13 through a cold air pipe 12, and the rear of the lower chamber of the experimental box 1 An air outlet 14 is provided on the upper right side of the side wall, an audio generator 15 is provided above the right side wall of the lower room of the test box 1, a push-pull cover plate 16 is provided above the upper room of the test box 1, and the movable supporting plate 2 is connected by a rotating shaft 17. At the central position of the horizontal axis at the junction of the upper chamber and the lower chamber of the experimental box 1, the center position of the movable pallet 2 is provided with a limit fixing device 18, as shown in Figures 3 and 4, the limit fixing device 18 includes a pressure sensor 180, a left Support 181, left arc block 182, right support 183, right arc block 184, first elastic band 185 and second elastic band 186, pressure sensor 180 is embedded in the central position of movable pallet 2, left support 181 and right support The seat 183 is fixedly connected to the left and right sides of the pressure sensor 180 respectively, the left arc block 182 and the right arc block 184 are slidably connected to the left support 181 and the right support 183 respectively, and one end of the first elastic band 185 is fixedly connected to the left support 181, one end of the second elastic band 186 is fixedly connected to the rear of the left support 181, the rear of the right support is provided with a first draw-in groove 187, and the front of the right support is provided with a second draw-in groove 188, which is elastically fixed by the elastic band For experimental mice, space for activities can be reserved, especially when the chest is pressed and stimulated, the mortality rate of experimental mice can be reduced. The right side of the limit fixture 18 is provided with an electroencephalogram monitoring device 19, as shown in Figures 3, 4, and 6, the electroencephalogram monitoring device 19 mainly includes a hemispherical electroencephalogram monitor 190, guide rail bars 191, baffle plates 192 and compression Spring 193, guide rail bar 191 are fixedly connected on the upper surface of movable pallet 2 and symmetrical about the horizontal axis center of movable pallet 2, the bottom surface of baffle plate 192 is fixedly connected on the upper surface of movable pallet 2, the left side of baffle plate 192 The side is fixedly connected with the right end face of the guide rail bar 191, the hemispherical brain wave monitor 190 is movably connected with the guide rail bar 191 through the chute block 194, and the compression spring 193 is connected between the hemispherical brain wave monitor 190 and the baffle plate 192, The hemispherical EEG monitor 190 is connected to the hemispherical EEG monitor 190 through the compression spring 193, so that the distance between the hemispherical EEG monitor 190 and the head can be elastically adjusted according to the size of the experimental mouse, with high fit and accurate measurement results. The left side of the electroencephalogram monitoring device 19 is provided with a temperature sensor 20, the right side of the electroencephalogram monitoring device 19 is provided with an oxygen concentration detection sensor 21, and the control room 3 is located on the right side of the experimental box 1, and the control room 3 is a right-angled trapezoid. An integrated controller 22 is provided inside the chamber 3, a motor 23 is provided on the left side of the integrated controller 22, a coupling 24 is connected above the motor 23, a corner reducer 25 is connected above the coupling 24, and the corner reducer 25 and The left end of rotating shaft 17 links to each other, is provided with locking member 26 between rotating shaft 17 and corner reducer 25, is provided with control panel 27 on the top surface of control chamber 3, as shown in Figure 1, 7, control panel 27 comprises display screen 270 , operation button plate 271, No. 1 connection hole 272 and No. 2 connection hole 273, display screen 270 is positioned at the top of operation panel 27, operation button plate 271 is positioned at the bottom left of display screen 27, No. 1 connection hole 272 and No. 2 connection hole 273 are located at the bottom right of the display screen 27 respectively, and the No. 1 connection hole 272 and the No. 2 connection hole 273 are connected with the electromagnetic proportional valve 10 and the refrigerator 13 through the wire one 100 and the wire two 130 respectively, and are connected through the No. 1 connection hole 272 and the No. The connection hole 273 is externally connected to the gas storage tank and the refrigerator, so as to realize centralized control. The power distribution room 4 is connected to the bottom of the control room 3, and the lifting compression device 5 is connected to the center position of the rear side wall of the experimental box 1. The lifting compression device 5 includes a lifting driver 51, a lifting support rod 52, an L-shaped connecting rod 53 and Pressing plate 54, the lifting support rod 52 is connected to the upper center position of the lifting driver 51, the horizontal section of the L-shaped connecting rod 53 is fixedly connected to the side of the lifting supporting rod 52, and the pressing plate 54 is fixedly connected to the vertical section of the L-shaped connecting rod 53. At the end, a cross bar 54 is movably connected to the top of the lifting support rod 52 , and a heating lamp 56 is arranged below the end of the cross bar 55 . As shown in Figures 1 and 2, a spotlight 57 is provided above the heating lamp 56, and the heating lamp is one of an incandescent lamp or a miniature ceramic heating lamp, and the number is one. The heat stimulation in the temperature stimulation is carried out.
本发明的工作方法为：先打开推拉盖板16，将实验鼠放置在限位固定装置18的中心位置，利用左弧块182和右弧块184初步固定，再利用第一松紧带185和第二松紧带186交叉固定，然后将实验鼠的头部放置到半球形脑电波监测器190内，选择刺激模式；当选择胸外压迫刺激时，通过升降驱动器51调节升降支撑杆52的高度，使得压板54与实验鼠胸部贴合，并进行一定力度的按压，按压过程中关注显示屏270中的脑电波信号，以此监测实验鼠的生理状况；当选择环境缺氧刺激时，将活动托板2通过电机23、连轴器24和拐角减速器25的作用翻转180度，盖上推拉盖板16，利用储气罐9向实验箱1内充入一定比例的二氧化碳与空气的混合气体，并利用氧浓度检测传感器21和半球形脑电波监测器190的反应情况联动调节实验箱1的缺氧度；当选择温度刺激模式时，先利用加热灯56和聚光罩57对实验鼠进行热刺激，然后将活动托板2翻转180度，利用制冷机13对实验鼠进行冷刺激，如此循环往复，并利用温度传感器20和半球形脑电波监测器190的反应情况联动调节实验箱1的温度；当选择光线刺激模式时，将活动托板2翻转180度，使实验鼠对准LED灯盘6，利用光线的明暗闪烁变化对实验鼠进行光线刺激，并利用半球形脑电波监测器190监测实验鼠的反应情况；当选择眩晕刺激模式时，利用电机23、连轴器24和拐角减速器25将固定在活动托板2上的实验鼠进行恒速或变速的上下翻转，并利用半球形脑电波监测器190监测实验鼠的反应情况。The working method of the present invention is: first open the push-pull cover plate 16, place the experimental mouse on the center position of the limit fixture 18, utilize the left arc block 182 and the right arc block 184 to initially fix, and then utilize the first elastic band 185 and the second The elastic band 186 is cross-fixed, and then the head of the experimental mouse is placed in the hemispherical EEG monitor 190, and the stimulation mode is selected; when external chest compression stimulation is selected, the height of the lifting support bar 52 is adjusted by the lifting driver 51, so that the pressing plate 54 Fit the chest of the experimental mouse, and press with a certain strength, pay attention to the brain wave signal in the display screen 270 during the pressing process, so as to monitor the physiological condition of the experimental mouse; The functions of the motor 23, the coupling 24 and the corner reducer 25 are turned over 180 degrees, and the push-pull cover plate 16 is covered, and a certain proportion of the mixed gas of carbon dioxide and air is filled into the test box 1 by using the gas storage tank 9, and the oxygen is used to The response of the concentration detection sensor 21 and the hemispherical brain wave monitor 190 is linked to adjust the degree of hypoxia in the experimental box 1; Turn the movable supporting plate 2 over 180 degrees, use the refrigerator 13 to cold stimulate the experimental mice, and repeat this cycle, and use the temperature sensor 20 and the response of the hemispherical brain wave monitor 190 to adjust the temperature of the experimental box 1; In the light stimulation mode, the movable support plate 2 is turned over 180 degrees, so that the experimental mouse is aimed at the LED lamp panel 6, and light stimulation is performed on the experimental mouse by using the light and dark flickering changes of the light, and the hemispherical brain wave monitor 190 is used to monitor the activity of the experimental mouse. Response situation; when the vertigo stimulation mode is selected, utilize the motor 23, the coupling 24 and the corner reducer 25 to turn the experimental rat fixed on the movable pallet 2 up and down at a constant or variable speed, and use hemispherical brain waves to monitor Device 190 monitors the response of the experimental mice.
最后应说明的是：以上实施例仅用以说明本发明的技术方案，而非对其限制；尽管参照前述实施例对本发明进行了详细的说明，本领域的普通技术人员应当理解：其依然可以对前述实施例所记载的技术方案进行修改，或者对其中部分技术特征进行等同替换；而这些修改或者替换，并不使相应技术方案的本质脱离本发明实施例技术方案的精神和范围。Finally, it should be noted that: the above embodiments are only used to illustrate the technical solutions of the present invention, rather than to limit them; although the present invention has been described in detail with reference to the foregoing embodiments, those of ordinary skill in the art should understand that: it can still be Modifications are made to the technical solutions described in the foregoing embodiments, or equivalent replacements are made to some of the technical features; these modifications or replacements do not make the essence of the corresponding technical solutions deviate from the spirit and scope of the technical solutions of the embodiments of the present invention.
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