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

发布时间：2018-09-06 08:47

【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;(2)TAC 2周组;(3)TAC 4周组;(4)TAC 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。
[Abstract]:Aim: to investigate the effects of monocarboxylate transporter 1 (monocarboxylate transporter 1 MCT1 on ventricular remodeling and heart failure after aortic arch constriction (transverse aortic coarctation,TAC) in mice, and to explore its possible mechanism. Methods: male C57BL/6 mice were divided into four groups: (1) sham operation group; (2) TAC 2 weeks group; (3) TAC 4 weeks group; (4) TAC 8 week group. Cardiac function was detected by echocardiography at the end of the 4th and 8th weeks. The expression of cleaved-caspase _ 3 and mitochondrial MCT1 protein in the myocardium was detected by colorimetric assay and the concentration of malondialdehyde (malondialdehyde,MDA) and lactic acid in the myocardium were detected by Western blot. Results: the results of cardiac hypertrophy in mice showed that cardiac hypertrophy appeared 4 weeks after TAC and severe heart failure occurred 8 weeks after TAC. The concentrations of lactic acid and MDA and the expression of cleaved-caspase 3 and MCT1 protein in myocardium of sham operation group, hypertrophic TAC 2 weeks group and heart failure TAC 4 weeks and 8 weeks group increased gradually. Compared with sham-operation group and TAC 2-week group, the expression of lactic acid and MDA in myocardium was significantly higher than that in sham-operated group and TAC 2-week group, and the expression of cleaved-caspase 3 and MCT1 protein were significantly increased. Conclusion Mitochondrial lactate shuttling mediated by MCT1 plays an important role in ventricular remodeling and heart failure, and its mechanism may include inducing oxidative stress and activating mitochondrial apoptosis pathway.
【作者单位】：南京医科大学第一附属医院心脏大血管外科;盐城市卫生职业技术学院;盐城市第一人民医院重症医学科;
【基金】：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)
【分类号】：R541.6

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