辛伐他汀对大鼠局灶性脑缺血的线粒体保护作用  

Protective Effect of Simvastatin on Mitochondrial in Rats with Focal Cerebral lschemia

作　　者：黄东轩[1] 陈燕豪[1] 莫沛[1] 郑晓和[2] 董晓先[4] 颜建云[3] 胡景鑫[3] 

机构地区：[1]广州医学院临床医学系,510182 [2]广州医学院检验医学系,510182 [3]广州医学院生理学教研室,510182 [4]广州医学院病理生理学教研室,510182

出　　处：《国际脑血管病杂志》2007年第5期372-375,共4页International Journal of Cerebrovascular Diseases

摘　　要：目的：探讨辛伐他汀对局部脑缺血损伤大鼠的保护作用及其线粒体机制。方法：96只大鼠随机分为假手术组、缺血再灌注组和辛伐他汀处理组，每组32只。建立大鼠大脑中动脉闭塞（MCAO）模型，观察大鼠神经功能、梗死体积、脑组织线粒体超微结构的改变；检测线粒体细胞色素c氧化酶（COX）、琥珀酸脱氢酶（SDH）活性，Ca^2＋含量，以及血清降钙素基因相关肽（CGRP）含量。结果：与假手术组相比较，缺血再灌注组各项指标均有显著改变；与缺血再灌注组比较，辛伐他汀能明显提高脑缺血大鼠的神经功能评分（P〈0．01），缩小梗死体积（P〈0．01），改善脑组织线粒体结构，并提高脑组织线粒体SDH活性（P〈0．05），提高COX活性（P〈0．01），降低脑组织线粒体Ca^2＋的含量（P〈0．01），提高血清CGRP水平（P〈0．05）。结论：辛伐他汀可能通过其抗氧化效应，提高脑组织线粒体SDH、COX活性及血清CGRP水平，减轻钙超载，缩小梗死体积，改善神经功能，从而对大鼠局灶性脑缺血起保护作用。Objective： To investigate the protective effect of simvastafin on focal cerelxal ischemia in rats and its mitochondrial mechanism. Methods： Ninety-six rats were randomly divided into sham operation, ischemia-reperfusion and simvastatin-treated groups （n = 32 in each group）. A model of middle cerebral artery occlusion （MCAO） in rats was established using the intraluminal thread method. The neurological function, the size of infarction and the changes of mitochondrial ultrastructure in brain tissues were evaluated. The activities of mitochondrial cytochrorne c oxidase （COX） and succinate dehydmgenase （SDH）, the concentration of Ca^2＋ and serum calcitma gene-related peptide （CGRP） v, ere measured. Results： All the indexes changed significantly in the ischemia-reperfusion group as compared with the sham operation group. Simvastatin could obviously improve the neurological function scores of focal cerebral ischemia rats （P 〈0. 01）, reduce the size of infarction （P 〈 0. 01）, improve the mitochondrial structure and increase the activities of SDH （P 〈0.05） and COX （P 〈0. 01）, decrease the concentration of mitochondrial Ca^2＋ （P 〈0. 01） in brain tissues, and elevate the levels of serum CGRP （P 〈 0. 05） as compared with the ischemia-reperfusion group. Conclusions： Simvastatin may irnprove the activities of SDH, COX and the levels of serum CGRP, reduce Ca^2＋ overload and the size of infarction, and irnprove neurological function through its antioxidation effect, and thus play a protective effect on focal cerebral ischemia in rats.

关 键 词：辛伐他汀 脑缺血 线粒体 神经保护 大鼠 

分 类 号：R74[医药卫生—神经病学与精神病学]