南京医科大学学报（自然科学版）2017，Vol.37Issue(5)：539-543,5.DOI:10.7655/NYDXBNS20170504
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
摘要
Abstract
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;② TAC 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.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Key words
monocarboxylate transporter 1/lactate shuttle/mitochondria/ventricular remodeling/heart failure分类
医药卫生引用本文复制引用
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（自然科学版）,2017,37(5):539-543,5.基金项目
国家自然科学基金(81573234) （81573234）
江苏省教育厅自然科学基金(12KJB320003) （12KJB320003）
江苏省中医局项目(LZ13217) （LZ13217）
