辛伐他汀对高脂血症大鼠心肌细胞内质网应激相关凋亡的影响.doc

1 辛伐他汀对高脂血症大鼠心肌细胞内质网应激相关凋亡的影响作者:周平李法琦张彬常晓东甘华陈力学【摘要】目的探讨辛伐他汀对高脂血症大鼠内质网应激( ERS ) 相关心肌细胞凋亡的影响及其机制。方法清洁级雄性 Wistar 大鼠 24 只,随机分为正常对照组( n=8 ,普通饲料饲养) ,高脂血症组( n=8 ,高脂饲料饲养) ,辛伐他汀组( n=8 , 高脂饲料+ 辛伐他汀 10 mg · kg-1 · d-1 灌胃饲养)。 12w 后,全自动化生化仪检测血清甘油三酯(TG) 及胆固醇(TC) 水平; HE 染色观察心肌组织的病理学变化; TUNE L 法检测心肌细胞凋亡;免疫组化法及 RT 拟 PCR 技术检测心肌细胞 ERS 信号通路分子——葡萄糖调节蛋白( GRP )78 的表达。结果与正常对照组相比,高脂血症组血清 TG 和 TC 水平、心肌细胞凋亡程度和 GRP78 表达水平均显著升高(P< 或P< ) ,且心肌组织结构异常;与高脂血症组比较,辛伐他汀组血清 TG 和 TC 水平、心肌细胞凋亡和 GRP78 表达水平均显著降低但仍高于正常对照组(P< ) 且心肌组织结构异常得到明显改善。结论高脂血症可以通 2 过激活 ERS 途径诱导心肌细胞凋亡并导致心肌组织结构异常, 辛伐他汀可能通过干预 ERS 途径抑制高脂血症诱导的心肌细胞凋亡并逆转其心肌组织的结构异常, 从而发挥心脏保护作用。【关键词】大鼠; 高脂血症; 内质网应激; 心肌细胞凋亡; 辛伐他汀 Effect of simvastatin on cardiomyocyte apoptosis induced by endoplasmic reticulum stress in rats with hyperlipidemia ZHOU Ping , LI Fa拟 Qi, ZHANG Bin , et al. Department of Gerontology , the First Affiliated Hospital of Chongqing Medical University , Chongqing 400016 , China 【 Abstract 】 Objective To investigate the cardioprotection and its mechanism of simvastatin on cardiomyocyte apoptosis induced by endoplasmic reticulum stress in rats with Twenty 拟 four male wistar rats were randomly divided into three groups : normal control group (n=8 , fed with normal diet) , high fat group (n=8 , fed!with high fat 3 diet ) and simvastatin group(n=8 , fed with high fat diet and recEived simvastatin 10mg · kg-1 · d-1 by gastric irrigation).After twelve weaks , the serum triglycerides (TG) and cholesterol (TC) levels were determined pletely automatic biochemistry pathological changes of myocardial tissue were detected by HE apoptotic cardiomyocytes of myocardial tissue were tested by expression of endoplasmic reticulum stress (ERS) associated molecle 拟 glucose regulated protEIn (GRP) 78 in myocardial tissue was investigated by immunohistochemistry and RT 拟 with normal control group , the serum TG and TC levels , and the numbers of apoptotic cardiomyocytes as well as the e