血管性痴呆小鼠海马线粒体复合体活性变化

Changes of mitochondrial complex activity in vascular dementia mice

目的:探讨血管性痴呆(VD)小鼠海马线粒体复合体活性变化。方法:抽取并回输约40%总血量加双侧颈总动脉夹闭20 min建立VD模型。病理学研究检测神经元损伤;分光光度计法检测丙二醛(MDA)含量、锰超氧化物歧化酶(Mn-SOD)活性和线粒体复合体活性;Western-blot检测Mn-SOD蛋白表达;Morris水迷宫评估学习记忆能力。结果:与假手术组相比,模型组学习记忆能力显著降低(P<0.05),MDA含量显著升高(P<0.05),Mn-SOD活性和蛋白表达显著降低(P<0.05);与假手术组相比,术后5 d模型组线粒体复合体Ⅰ、Ⅱ、Ⅲ、Ⅳ活性显著降低(P<0.05),术后15,30 d和60 d模型组线粒体复合体Ⅰ、Ⅱ活性无显著变化(P>0.05),复合体Ⅲ、Ⅳ活性显著降低(P<0.05);病理学检测显示模型组海马出现进行性神经元损伤。结论:线粒体复合体III、IV活性异常可能是VD的发病机制之一。

OBJECFIVE To investigate changes of mitochondrial complex activity in vascular dementia （VD） mice. METHODS VD model was established through drawing out and reperfusing 40% of whole blood volume plus clamping carotid arteries of mice for 20 min. Histological observation was performed to evaluate neural damage. Malonaldehyde （MDA）, manganese superoxide dismutase （Mn-SOD） and mitochondrial complex activity were determined by using spectrophotometer. Expression of Mn-SOD was tested by western blot, learning and remembering ability were determined by Morris water maze. RESULTS Comparedwith sham operation group, MDA level was increased in I/R group （P〈0. 05）. Activity and expression of Mn-SOD, learning and remembering ability were decreased in mice in model group （P〈0. 05）. Activities of mitochondrial complex Ⅰ , Ⅱ, Ⅲ and Ⅳ in model group were lower than those in sham operation group in the 5 th day （P〈0. 05）. In the 15th, 30 th and 60 th days, activities of complex Ⅲ and Ⅳ of model group were lower than those in sham operation group （P 〈0. 05）, but no significant difference was observed between model group and sham operation group in complex Ⅰ and Ⅱ activities （P〉0. 05）. Progressive neural damages were observed in model group. CONCLUSION Abnormal activities of mitochondrial complex Ⅲ and Ⅳ may be involved in mechanisms of VD.