脊髓半侧液压损伤大鼠动物模型的建立及评估

发布时间：2018-04-30 23:32

本文选题：脊髓半侧液压损伤 + 动物模型　；参考：《天津医科大学》2007年博士论文

【摘要】： 目的：1、开发小动物立体定向固定系统和适合制备小动物脊髓半侧损伤模型的打击管及连接装置。2、建立小动物脊髓半侧损伤标准化的操作方法。3、使用国际通用的液压冲击损伤仪，建立一种损伤能量精确、重复性好、损伤分级明确、并发症和死亡率低的脊髓半侧损伤模型。4、建立评价脊髓半侧损伤动物模型的理想评价指标(包括行为、电生理、影像、病理)。为深入研究脊髓损伤后的病理、生理变化过程及治疗效果的验证提供稳定的实验平台。方法：1、64只SD大鼠分为损伤组(n=48)，对照组(n=16)，损伤组按照损伤能量分为轻、中、重3个亚组(每组n=16)。2、所有大鼠均采用标准手术步骤操作，行T10右侧椎板开骨窗。3、大鼠固定于自行开发的小动物实验立体定向固定系统，连接打击管道，密封排水，利用液压打击系统在特定打击能量下制作轻、中、重各级脊髓损伤模型。4、各组于建模后3、7、14天各取3只动物行实验性脊髓损伤神经功能评分、运动诱发电位、磁共振、病理检查及免疫组化检查，对模型进行评价；另7只动物行连续观察至14天，进行动态评估。结果：1、本研究开发的小动物立体定向固定系统具有操作简单固定可靠的特点，可保证大鼠在麻醉清醒后牢固固定，并确保致伤打击方向一致，打击管及连接管道密闭性良好，避免了打击过程中因漏水而发生致伤力衰减。2、脊髓损伤节段准确，根据损伤能量的不同可稳定地分别制备出轻、中、重型脊髓半侧损伤模型，各组间神经功能评分、运动诱发电位评价指标与损伤程度显著相关，且各组间上述指标具的差异具有统计学意义(P＜0.05)。磁共振、病理结果可明确显示不同程度的伤后改变。3、随时间延长模型动物神经功能可部分恢复。4、本组动物损伤后的自然死亡率为8％，尿储留等并发症发生率为14％，相对较少。结论：1、自行研制的小动物立体定向固定系统和小动物脊髓损伤专用打击管及连接装置稳定性好，可使液压损伤能量按设计方向精确地作用于脊髓的特定位置，提高了模型的准确性和可重复性。2、本研究建立的脊髓半侧液压损伤动物模型较为接近人体脊髓损伤自然过程，，并且能够精确控制损伤能量，较好地制备出不同程度的脊髓半侧损伤模型。3、采用神经功能评分、运动诱发电位、磁共振、病理检查方法可对损伤程度和恢复状况进行精确评估。4、该方法保留部分二便功能，并发症少，动物长期存活率高。
[Abstract]:Objective: to develop a stereotactic fixation system for small animals, and to establish a standardized operating method of spinal cord injury in small animals by using the universal hydraulic impingement instrument, which is suitable for the establishment of a small animal spinal cord injury model and its connecting device .2.The purpose of this paper is to establish a standardized operation method of spinal cord injury in small animals. To establish a spinal cord injury model with accurate energy, good reproducibility, clear injury grade, low complication and mortality, and to establish an ideal evaluation index (including behavior, electrophysiology, imaging) for evaluating the animal model of spinal cord hemilateral injury. Pathology. To provide a stable experimental platform for the further study of pathology, physiological process and therapeutic effect of spinal cord injury. Methods Sixty-four Sprague-Dawley rats were divided into injury group (n = 48) and control group (n = 16). The rats were fixed to the experimental stereotactic fixation system of small animals developed by ourselves, connected to the striking pipe, sealed and drained, and made light, medium and light by hydraulic hitting system under the specific strike energy, the rats were fixed on the right side of the vertebral lamina of T10, and the rats were fixed in the experimental stereotactic fixation system developed by ourselves. The model of spinal cord injury was severe. 3 animals were taken from each group on the 3rd day and 14th day after modeling to evaluate the experimental spinal cord injury nerve function score, motor evoked potential, magnetic resonance imaging, pathological examination and immunohistochemical examination. The other 7 animals were observed for 14 days for dynamic evaluation. Results: the stereotactic fixation system of small animals developed in this study has the characteristics of simple and reliable operation, which can ensure that the rats can be firmly fixed after anaesthesia, and ensure that the direction of injury is the same, and the airtight of the pipe and the connecting pipe is good. The injury force decreased by 0.2 due to leakage during the attack, and the segment of spinal cord injury was accurate. According to the different energy of injury, the models of light, medium and severe spinal cord injury could be made stably, and the neurological function scores of each group could be obtained. The evaluation index of motor evoked potential was significantly correlated with the degree of injury, and the difference of the above indexes among the groups was statistically significant (P < 0.05). Magnetic resonance imaging (MRI), pathological results showed the changes of different degrees after injury. The neurological function of model animals recovered partly with time. The natural mortality rate was 8, and the incidence of complications such as urinary retention was 14, relatively less. Conclusion the self-developed stereotactic fixation system for small animals and the special hitting tube and connecting device for spinal cord injury in small animals have good stability and can make the hydraulic injury energy act precisely on the specific position of spinal cord according to the design direction. The accuracy and repeatability of the model were improved. The animal model of spinal cord hemiplegic injury established in this study is close to the natural process of spinal cord injury and can accurately control the injury energy. The model of spinal cord hemilateral injury with different degrees was made. The nerve function score, motor evoked potential, magnetic resonance and pathological examination can be used to accurately evaluate the degree of injury and recovery. There are few complications and high long-term survival rate.
【学位授予单位】：天津医科大学
【学位级别】：博士
【学位授予年份】：2007
【分类号】：R651.2;R-332

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