文章摘要
黄 诚,吕洪臻,司林杰,王晓伟.线粒体乳酸穿梭对小鼠主动脉弓缩窄术后心室重构和心力衰竭的影响[J].南京医科大学学报,2017,(5):539~543
线粒体乳酸穿梭对小鼠主动脉弓缩窄术后心室重构和心力衰竭的影响
The effect of mitochondrial lactate shuttle on myocardial remodeling and heart failure induced by aortic constriction in mice
投稿时间:2016-12-17  
DOI:10.7655/NYDXBNS20170504
中文关键词: 单羧酸转运蛋白1  乳酸穿梭  线粒体  心室重构  心力衰竭
英文关键词: monocarboxylate transporter 1  lactate shuttle  mitochondria  ventricular remodeling  heart failure
基金项目:国家自然科学基金(81573234);江苏省教育厅自然科学基金(12KJB320003);江苏省中医局项目(LZ13217)
作者单位
黄 诚 南京医科大学第一附属医院心脏大血管外科江苏 南京 210029盐城市卫生职业技术学院江苏 盐城 224000 
吕洪臻 盐城市卫生职业技术学院江苏 盐城 224000 
司林杰 盐城市第一人民医院重症医学科江苏 盐城 224000 
王晓伟 南京医科大学第一附属医院心脏大血管外科江苏 南京 210029 
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中文摘要:
      目的:研究单羧酸转运蛋白1(monocarboxylate transporter 1,MCT1)介导的线粒体乳酸穿梭对小鼠主动脉弓缩窄术(transverse aortic coarctation,TAC)后心室重构和心力衰竭的影响,并探讨其可能的机制。方法:本实验采用雄性C57BL/6小鼠,实验分为4组:①假手术组;②TAC 2周组;③TAC 4周组;④TAC 8周组。TAC术建立小鼠动物模型,分别于术后第2周末、第4周末和第8周末使用心脏超声检测小鼠心功能,比色法测定心肌组织内乳酸及丙二醛(malondialdehyde,MDA)浓度,Western blot检测心肌胞质cleaved-caspase 3和线粒体MCT1蛋白的表达。结果:小鼠心超结果显示TAC术后2周出现明显心肌肥厚,TAC术后4周出现心力衰竭,TAC术后8周出现严重心力衰竭。假手术组、心肌肥厚的TAC 2周组及心力衰竭的TAC 4周、8周组心肌组织中乳酸和MDA浓度以及cleaved-caspase 3和MCT1蛋白表达逐渐升高。与假手术组和TAC 2周组相比,TAC 4周和8周组心肌组织中乳酸和MDA浓度、cleaved-caspase 3和MCT1蛋白的表达均明显升高。结论:MCT1介导的线粒体乳酸穿梭在心室重构和心力衰竭发生发展过程中起着重要的作用,其机制可能包括诱导氧化应激和活化线粒体凋亡通路。
英文摘要:
      Objective:To determine the effect and mechanisms of monocarboxylate transporter 1(MCT1)-mediated mitochondrial lactate shuttle on ventricular remodeling and heart failure induced by transverse aortic constriction(TAC) in mice.Methods:An animal model of cardiac hypertrophy was created by TAC in male C57BL/6 mice.Cardiac dimensions and functions were evaluated by echocardiography after 2 weeks,4 weeks, and 8 weeks following TAC,respectively.There were four groups:①Sham-operate group;②TAC 2 weeks group;③TAC 4 weeks group;④TAC 8 weeks group.Intracellular lactate and malondialdehyde(MDA)were measured by colorimetric,the proteins expression of cleaved-caspase 3 and MCT1 were detected by Western blot.Results:As echocardiography evaluation,the mice exhibited cardiac hypertrophy after TAC 2 weeks,heart failure after TAC 4 weeks,and severe heart failure after TAC 8 weeks.An increasing gradient of lactate and MDA concentrations,as well as cleaved-caspase 3 and MCT1 protein expressions were identified in the sham,TAC 2 weeks,and TAC 4 and 8 weeks groups.Besides,the concentrations of lactate and MDA and expressions of cleaved-caspase 3 and MCT1 were also found higher in the TAC 4 and 8 weeks groups than those of the sham and TAC 2 weeks groups.Conclusions:MCT1-mediated mitochondrial lactate shuttle plays an important role in the development of myocardial remodeling and heart failure.The molecular mechanisms may be through inducing oxidative stress and activating mitochondrial control of apoptosis.
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