Parkin介导的线粒体自噬对1型糖尿病急性心肌梗塞早期损伤的保护作用  

The Protective Role of Parkin Mediated Mitophagy in a Mouse Model of Type 1 Diabetes Combined with Acute Myocardial Infarction

作　　者：李娜[1] 余文军[1] 贾红兵 王佳兴[1] 李聪叶[1] 张荣庆[1] 张英梅[1] 王海昌[1] 

机构地区：[1]第四军医大学西京医院心血管内科,陕西西安710032 [2]解放军323医院干一科,陕西西安710032

出　　处：《现代生物医学进展》2015年第32期6201-6205,6282,共6页Progress in Modern Biomedicine

基　　金：国家自然科学基金项目(31171090)

摘　　要：目的:观察线粒体自噬在急性心梗(MI)早期的变化及对1型糖尿病(DM)小鼠心肌急性缺血损伤的影响。方法:将100只健康雄性C57BL/6小鼠随机分为5组,对照+假手术组(CS组);1型糖尿病+假手术组(DS组);对照+心肌梗死组(CMI组);1型糖尿病+心肌梗死组(DMI组);1型糖尿病+心肌梗死组+Parkin腺病毒过表达组(DMIPO组),每组20只。检测和比较各组小鼠的心脏功能,心肌梗死面积,心肌细胞凋亡,自噬小体含量以及心肌组织中Parkin和LC3的表达量变化。结果:与CS组相比,CMI组自噬小体含量增多,LC3II的表达量上调,Parkin的表达量明显上调(P<0.05)。与CMI组比,DMI组小鼠心功能下降加剧,心梗面积增大,心肌细胞凋亡数量明显增加(P<0.05),自噬水平未见明显升高。DMIPO组较DMI组自噬水平升高,心肌梗死面积减小(P<0.05),心肌细胞凋亡数量减少(P<0.05),心功能改善。结论:1型糖尿病通过抑制Parkin介导的心肌线粒体自噬增加心肌急性缺血损伤易感性,上调Parkin的表达可以减轻1型糖尿病时急性缺血性心肌损伤。Objective： To explore the role of mitophagy in the acute myocardial infarction and the effect of diabetes on autophagy and mitophagy in mice with acute ischemic injury. Methods： 100 male C57BL/6 mice were randomly divided into 5 group： Control ＋Sham （CS）; Diabetes＋Sham （DS）; Control＋Myocardial infarction （CMI）; Diabetes＋Myocardial infarction （DMI）; Diabetes＋Myocardial infarction＋Adenovirus Parkin Overexpression （DMIPO）. Cardiac fimction, myocardial infarct area, myocardial apoptosis, autophagosome content,and expression of LC3 and Parkin were evaluated. Results： Autophagy was markedly increased in CMI group compared with CS group as indicated by increased autophagosome content, LC3II and Parkin expression. DMI group presented a severe cardiac dysfunction with enlarged infarct size and increased cell apoptosis （P〈0.05） compared with CMI group, autophagy in DMI group didn＇t present an increased level. DMI ＋Parkin overexpression group exhibited an improvement in cardiac function along with increased mitophagy and decreased apoptosis. Conclusions： Diabetic heart is more vulnerable to acute ischemic injury via the inhibition of Parkin mediated mitophagy. Overexpression of Parkin up-regulated mitophagy and alleviated acute ischemic injury in diabetes mice.

关 键 词：1型糖尿病 急性心梗 自噬 线粒体自噬 

分 类 号：R587.2[医药卫生—内分泌] R542.22[医药卫生—内科学]