线粒体氧化对血管性痴呆大鼠神经功能的损伤及其作用机制

Effect of mitochondrial oxidative lesion in neurological function and its mechanism in rats with vascular dementia

目的:探讨线粒体氧化损伤在血管性痴呆(VD)大鼠发病机制中的作用,为VD的治疗提供理论依据。方法:采用双侧颈总动脉永久结扎方法,制备慢性脑缺血致VD大鼠模型。大鼠分为正常对照组(假手术组)、缺血1月及2月模型组,采用Morris水迷宫进行大鼠记忆功能测定;提取大鼠海马线粒体采用紫外分光光度计及荧光分光光度计检测线粒体超氧化物歧化酶(SOD)活性、丙二醛(MDA)含量及线粒体膜流动性。结果:缺血1月、2月模型组与假手术组比较逃避潜伏期明显延长(P<0.05),缺血1月及2月模型组SOD活性均低于正常对照组(P<0.05),MDA含量高于正常对照组(P<0.05),线粒体膜黏滞系数高于正常对照组(P<0.05)。结论:VD发病与海马线粒体SOD、MDA的代谢及线粒体膜流动性有关,即与线粒体氧化应激有关,VD大鼠可能通过清除自由基减轻神经功能损伤而改善学习记忆功能,提示线粒体氧化损伤可能是VD的发病机制之一。

Objective To study the effect of the mitochondrial oxidative lesion in the pathologic mechanism of vascular dementia （VD） in rats, and provide theoretical basis for treatment of VD. Methods The VD rat model through ligating bilateral occlusion of both common carotid arteries was made. The rats ware divided into sham group, ischemia-1-month group, and ischemia-2-month group. The pathologic and histologic changes of rats after Morris Water Maze and place navigation were determined. The SOD activity and the MDA content were measured by UV-spectrophotometer and the fluidity of mitochondrial membrane was detected by fluorescence spectrophotometer. Results Compared with sham group, the escape latencies in ischemia-1-month and ischemia-2- month group were prolonged significantly （P〈0.05）, the SOD activity was decreased significantly （P〈0.05）, the MDA content and the viscous coefficient （η） of mitochondrial membrane were significantly increased （P〈 0.05）. Conclusion The pathologic mechanism in VD rats is concerned with the metabolism of SOD and MDA and the fluidity of mitochondrial membrane, and is related to the mitochondrial oxidative stress. Above all, mitochondrial oxidative lesion may be one of pathologic mechanism of VD.