辛伐他汀通过Akt/ GSK3β通路抑制心肌梗死后心肌细胞凋亡  

Inhibitory effect of simvastatin on cardiomyocyte apoptosis through Akt/GSK3β pathway after myocardial infarction

作　　者：叶强[1,2] 陈良海[1] 刘应才[1] 黄维义[1] 刘乾惠[1] 黄永丽[1] 张茂惠[3] 雷寒[2] 覃数[2] 

机构地区：[1]泸州医学院附属医院心血管内科,四川泸州646000 [2]重庆医科大学附属第一医院心血管内科,重庆400016 [3]重庆医科大学附属第二医院超声科,重庆400016

出　　处：《中国药理学通报》2011年第12期1656-1660,共5页Chinese Pharmacological Bulletin

基　　金：重庆自然科学基金资助项目(渝科发计字[2004]54号文)

摘　　要：目的观察辛伐他汀对心肌梗死后心肌细胞凋亡的影响并探讨其分子机制。方法结扎大鼠左冠状动脉前降支建立心肌梗死模型。实验组给予药物处理(辛伐他汀40mg.kg-1),10 d后,超声心动图检测左心室功能参数,生化法检测血脂水平,TUNEL法检测心肌组织中的凋亡心肌细胞,Western blot法检测p-Akt ser473、p-GSK3βser9和β-cate-nin蛋白表达。结果辛伐他汀组TC、LDL-C及TG水平与心肌梗死组比较无差异(P>0.05),辛伐他汀组较心肌梗死组在梗死周边区、远离梗死区心肌细胞凋亡明显减少(P<0.05),左心室功能改善(P<0.05),辛伐他汀上调p-Aktser473、p-GSK3βser9和β-catenin蛋白表达。结论辛伐他汀改善心肌梗死后心功能,可能是通过激活Akt/GSK3β通路,抑制心肌细胞凋亡实现。Aim To investigate the inhibitory effect of simvastatin on cardiomyocyte apoptosis and potential molecular mechanisms after myocardial infarction. Methods Simvastatin was administered to the rats with myocardial infarction which was modeled by left anterior descending coronary artery ligation. After 10 days, the apoptotic cardiomyocyte cells were quantified by TUNEL staining; left ventricular function index was measured by echoeardiography and the level of serum lipid was measured by biochemical method; the protein level of p-Akt set473, p-CSK3β set9 and β-catenin were detected by western blot. Results Compared with myocardial infarction group, apoptotie cardiomyocyte cells in simvastatin group significantly decreased in border zone and non-infarction zone （ P 〈 0. 05 ） and left ventricular function was improved significantly （P 〈 0.05 ）. There was no difference in the serum levels of TC, LDL-C and TG between myocardial infarction group and simvastatin group （ P 〉 0.05 ） ; the protein levels of p-Akt ser473, p-GSK3β ser9 and β-catenin were upregulated by simvastatin. Conclusions Simvastatin improves cardiac function after myocardial infarction through inhibiting cardiomyocyte apoptosis through Akt/GSK3β pathway.

关 键 词：辛伐他汀 心肌梗死 心肌细胞 心功能 凋亡 AKT GSK3Β 

分 类 号：R-332[医药卫生] R322.11