改良双侧颈总动脉结扎法与传统法制备的大鼠慢性脑缺血模型比较

摘要

目的:比较改良的双侧颈总动脉结扎法与传统的双侧颈总动脉结扎法(2-VO法)制作的大鼠慢性灌注不足引起的血管性痴呆(VD)模型的学习记忆能力、海马区及纹状体形态学和大鼠术后的死亡率变化.验证是否改良的2-VO法优于传统的造模方法.方法:采用双侧颈总动脉结扎法造成大鼠永久慢性大脑灌注不足导致的VD模型.雄性2月龄SD大鼠48只,随机分为传统2-VO组20只,改良2-VO组20只和假手术组8只.传统组同时结扎双侧颈总动脉；改良组先结扎右侧颈总动脉,1周后再次结扎左侧的颈总动脉.在术后48h和60d记录各组的存活率,2个月后进行水迷宫试验来测定大鼠的空间学习记忆和运动能力.水迷宫试验结束后处死大鼠,观察海马和纹状体的形态学变化.结果:改良组与传统组大鼠术后48h及60d的死亡率比较都明显降低(P＜0.05).两种模型组大鼠学习记忆能力与假手术组比较差异有显著性(P＜0.01),而两种模型大鼠组间学习记忆功能差异无显著性(P＞0.05).各组大鼠的运动功能比较无明显差异性(P＞0.05).两种模型组大脑海马区及纹状体均发生明显病理形态学改变.结论:改良2-VO法可以复制大鼠大脑永久性慢性灌注不足引起的VD模型,引起与记忆有关的海马及纹状体损害,而运动功能未见损害.改良2-VO法和传统的方法在VD造模上没有本质的区别,但大鼠的存活率明显提高.%Objective: To compare the changes of cognitive abilities, hippocampal synapse and striatum morphology, and postoperation death rates of vascular dementia(VD) rat models caused by chronic cerebral hypoperfusion, by using modified bilateral common carotid arteries ligation(2-VO) method and standard 2-VO method respectively, and to verify if the modified 2-VO method was better than the standard 2-VO method in establishing VD rat model. Method: VD rat models caused by permanent chronic brain hypoperfusion, by means of 2-VO method were a dopted. Male Sprague Dawley(SD) rats (n=48), aged 2 months, were randomly divided into modified 2-VO group(n= 20), standard 2-VO group(n=20) and sham-operation group(n=8). In the standard 2-VO group, bilateral common carotid arteries were ligated at the same time; in the modified 2-VO group, right side common carotid arteries were ligated at first, 1 week later, left side arteries then ligated. Each group's survival rate was respectively recorded after 48h and 60d, and spatial learning, memory and motor abilities were measured with Morris water maze test two months later, after which, the rats were sacrificed to observe the morphological damages of hippocampal synapse and striatum.Result: The death rates in modified 2-VO group and standard 2-VO group after 48h and 60d declined obviously (P<0.05). Compared with sham-operation group, the spatial learning and memory abilities in the two model- groups presented distinct differences(P<0.01), but rare difference between the two groups(P>0.05). There was no significant difference in motor function among the three groups(P>0.05) but distinct pathomorphology changes appeared in hippocampal synapse and striaturn of the two model groups.Conclusion: Modified 2-VO method can duplicate VD model caused by permanent chronic brain hypoperfusion, resulting in the damage of hippocampal synapse and striaturn related to memories, but no injuries in motor function. There is no substantial difference between the modified 2-VO method and the standard 2-VO method in establishing VD models, but survival rate in modified 2-VO group rises remarkably.