大鼠血管性痴呆模型海马组织中线粒体的变化

目的:观察血管性痴呆模型(Vascular dementia,VD)大鼠海马组织内线粒体超微结构、线粒体膜电位与空间学习记忆能力的变化。方法:健康成年雄性Wistar大鼠30只,随机分为假手术组(SHAM)和血管性痴呆(VD)组,每组15只。VD组行双侧颈总动脉结扎手术制备血管性痴呆动物模型,SHAM组手术步骤同VD组,但不结扎颈总动脉。于术后第29天起行Morris水迷宫测试大鼠空间学习记忆功能,第1-5天为定位航行试验,评估大鼠空间学习能力,第6天进行空间探索试验,评估大鼠空间记忆功能。采用透射电镜技术、流式细胞学技术分别检测大鼠海马组织线粒体形态和功能变化。结果:与SHAM组相比,血管性痴呆模型组大鼠Morris水迷宫试验中逃避潜伏期明显延长(P0.01),在目标象限中停留时间显著缩短(P0.01),空间学习记忆能力受损,血管性痴呆模型组大鼠海马组织线粒体超微结构有明显损伤,线粒体膜电位明显下降(P0.01)。结论:线粒体损伤是血管性痴呆空间学习记忆功能障碍的重要机制之一。

The Changes of Mitochondria in Hippocampus of Vascular Dementia Rats

Objective:To observe the changes of ultrastructure, ROS, and mitochondrial membrane potential in mitochondria of hippocampus, and the alteration in spatial learning and memory function of vascular dementia (VD) rats.Methods:Thirty healthy adult male Wistar rats were randomly assigned into two groups, SHAM group and vascular dementia (VD) group, with 15 rats in each group. Bilateral common carotid arteries occlusion was used in healthy adult male Wistar rats to establish VD model. Rats in SHAMgroup were operated similarly to VD group without occlusion of common carotid arteries. Spatial learning and memory deficits were tested by Morris water maze. The acquisition test was performed for five consecutive days beginning from the 29th day after the operation. Escape latency was recorded to evaluate spatial learning. On the sixth day, probe trials were assessed, and the time spent in the target quadrant where the platform had been located was recorded to evaluate spatial memory. The changes of mitochondria in hippocampus were detected by transmission electron microscopy and flow cytometry.Results:In the Morris water maze, rats in the VD group exhibited significantly prolonged escape latency (P<0.01) and spent significantly less time in the target quadrant (P<0.01) as compared to the control group. In hippocampus of the VD group rats, the ultrastructure of mitochondria was markedly damaged, and the mitochondrial membrane potential was significantly decreased (P<0.01).Conclusion:In vascular dementia rats, mitochondrial damage plays an important role in the pathogenesis of spatial cognitive impairment.