辛伐他汀通过Akt/eNOS途径改善心肌梗死后急性期心功能  

Simvastatin improves cardiac function in acute phase after myocardial infarction through Akt/eNOS pathway

作　　者：朱乔燕 王光宇[1,2] 毕亚光 张庆勇[1] 魏盟[1] 

机构地区：[1]上海市第六人民医院心血管内科,上海200233 [2]上海交通大学医学院,上海200233

出　　处：《中国药理学通报》2015年第10期1375-1379,共5页Chinese Pharmacological Bulletin

基　　金：上海自然科学基金资助项目(No 13ZR1431500)

摘　　要：目的探讨辛伐他汀(simvastatin,Sim)对急性心肌梗死后心肌内源性抗氧化系统的影响及其潜在机制。方法应用结扎大鼠冠状动脉左前降支的方法模拟急性心肌梗死(AMI),随机分为心肌梗死组(MI)组和辛伐他汀组(Sim,20mg·kg-1·d-1),另设假手术组(Sham组)。Sim组连续灌胃7 d,MI组和Sham组给予等剂量的生理盐水灌胃。7 d后,观察心肌血流动力学参数变化;检测血脂及心肌坏死标记物肌钙蛋白I(c-Tn I)和乳酸脱氢酶(LDH)变化;ELISA法检测心肌抗氧化系统超氧化物歧化酶(SOD)及谷胱甘肽过氧化物酶(GP)水平。Western blot检测心肌p-Akt/p-e NOS蛋白表达变化。结果急性心肌梗死明显降低心肌血流动力学参数,增加血清c-Tn I和LDH水平,降低SOD及GP水平,降低p-Akt和p-e NOS蛋白表达。Sim组能明显改善急性期心功能恶化,减低血清c-Tn I和LDH水平,增加SOD及GP水平,增加p-Akt和p-e NOS蛋白表达。结论急性心肌梗死后早期应用Sim能明显改善心功能,增加心肌抗氧化系统活性,减少心肌坏死,这可能与提高p-Akt和p-e NOS蛋白表达有关。Aim To investigate the effect of simvastatin ( Sim ) on endogenous antioxidant system after acute myocardial infarction ( AMI ) and its potential mecha-nisms. Methods The acute myocardial infarction ( AMI ) rat models were made by ligation left anterior descending of coronary artery. Then the successful models were randomly divided into myocardial infarc-tion group ( MI group) and simvastatin group ( Sim,20 mg·kg-1·d-1), another group without ligation left anterior descending of coronary artery served as sham group(Sham group). The Sim group was administered simvastatin by gavage for 7 days. MI group and Sham group received saline. Hemodynamic parameters, lipid levels, troponinI ( c-TnI ) and lactate dehydrogenase ( LDH) concentrations were examined after 7days, and the levels of superoxide dismutase ( SOD) and glutathi-one peroxidase ( GP) of myocardial antioxidant system were detected by ELISA. The expression of cardiac p-Akt and p-eNOS protein were detected by Western blot. Results Acute myocardial infarction significant-ly lowered cardiac hemodynamic parameters, increased serum c-TnI and LDH levels, lowered levels of SOD and GP, and lowered the expression of p-Akt and p-eNOS protein. However, Sim could effectively prevent the deterioration of cardiac function, reduce serum c-TnI and LDH levels, increase levels of SOD and GP, and increase p-Akt and p-eNOS protein expression. Conclusion Early using Sim can effectively improve heart function after acute myocardial infarction, acti-vate myocardial antioxidant system,and reduce myocar-dial necrosis, which may be related to increasing the expression of p-Akt and p-eNOS.

关 键 词：辛伐他汀 心肌梗死 心功能 氧化应激 急性期 P-AKT p-eNOS 

分 类 号：R-332[医药卫生] R322.11