活化的自噬在2周糖尿病大鼠和糖尿病患者心肌缺血后适应中作用研究  

Effects of activated autophagy on 2 weeks after diabetic rats and diabetic patients with myocardial ischemic postconditioning

作　　者：魏超[1] 李红霞[1] 韩莲花[1] 杨向军[1] WEI Chao;LI Hongxia;HAN Lianhua;YANG Xiangjun(Department of Cardiology,the First Affiliated Hospital of Soochow University,Suzhou 215007,China)

机构地区：[1]苏州大学附属第一医院心内科,江苏苏州215007

出　　处：《东南大学学报（医学版）》2018年第4期597-601,共5页Journal of Southeast University(Medical Science Edition)

基　　金：江苏省科技项目(BL2014050)

摘　　要：目的:研究自噬在2周糖尿病大鼠和糖尿病患者心肌缺血后适应(IPost)中活性的变化及其作用。方法:采用2周糖尿病(D)大鼠和2周糖尿病胰岛素治疗(D+I)大鼠建立心肌缺血再灌注模型,计算心肌梗死面积,行电镜和Western blot检测自噬活性变化,运用自噬抑制剂(3-MA)研究自噬在IPost中的作用;用RT-PCR检测患者自噬相关基因表达水平。结果:IPost能升高大鼠心肌自噬活性,显著减少大鼠心肌梗死面积;3-MA抑制自噬活性后,大鼠心肌梗死面积显著升高(P<0.05),Bad表达显著升高,而Bcl-2表达明显降低(P<0.05)。IPost升高患者术后自噬相关基因表达水平(P<0.05),48 h达到高峰。结论:IPost活化的自噬在2周D大鼠和2周D+I大鼠对心肌起保护作用;IPost升高患者自噬相关基因表达水平。Objective： To evaluate the activation and contribution of autophagy to ischemia postconditioning（ IPost） in 2 weeks after diabetic rat hearts and diabetic IPost patients. Methods： The model of rat myocardial ischemia and reperfusion was established on 2-week diabetes mellitus（ D） rats and diabetic insulin therapy（ D ＋ I）rat hearts. The myocardial infarct size was calculated. The activation of autophagy was observed under electron microscopy and Western blot after 120 min reperfusion. The role of autophagic mechanisms in IPost was studied by coadministration of the autophagy inhibitor 3-methyladenine（ 3-MA）. The levels of autophagy related genes were detected by RT-PCR in patients. Results： In IPost rat hearts,the area of myocardial infarction was obviously decreased,the activation of autophagy increased significantly. But after 3-MA co-administration,the area of myocardial infarction was significantly increased（ P〈0. 05）. The expression of Bad protein was obviously increased. The levels of Bcl-2 protein was obviously decreased（ P〈0. 05）. The expression level of autophagy related genes was significantly increased in patients（ P〈0. 05）. 48 hours to reach the peak. Conclusion： In 2-week D rat and 2-week D ＋ I rat,the protective effects of IPost are associated with the activation of autophagy. In diabetic patients with acute myocardial infarction,IPost increases autophagy gene expression levels.

关 键 词：自噬 心肌缺血后适应 糖尿病 微管相关蛋白1轻链3 BECLIN 1 

分 类 号：R-33[医药卫生] R587.1