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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。
Objective: To investigate the effect of monocarboxylate transporter 1 (MCT1) -mediated mitochondrial lactic acid shuttle on ventricular remodeling and heart failure after transverse aortic coarctation (TAC) in mice and to explore its possible role Mechanisms. Methods: Male C57BL / 6 mice were used in this experiment. The experiment was divided into 4 groups: (1) sham operation group; (2) TAC 2 weeks group; (3) TAC 4 weeks group; (4) TAC 8 weeks group. TAC was used to establish mouse model of heart function. Cardiac function was measured by cardiac echocardiography at the 2nd, 4th and 8th week after operation respectively. Lactic acid and malondialdehyde (MDA) concentrations were measured by colorimetry. The expressions of cleaved-caspase 3 and mitochondrial MCT1 in myocardium were detected by Western blot. Results: The results of cardiac ultrasonography showed obvious cardiac hypertrophy 2 weeks after TAC, heart failure 4 weeks after TAC, and severe heart failure 8 weeks after TAC. The concentration of lactate and MDA, the expression of cleaved-caspase 3 and MCT1 protein in myocardial tissue in sham operation group, TAC 2 weeks group with cardiac hypertrophy and TAC 4 weeks and 8 weeks after heart failure group increased gradually. Compared with the sham operation group and the TAC 2-week group, the concentrations of lactic acid and MDA, the expressions of cleaved-caspase 3 and MCT1 protein in myocardial tissue of 4 weeks and 8 weeks of TAC were significantly increased. Conclusion: MCT1-mediated mitochondrial lactate shuttle plays an important role in the development of ventricular remodeling and heart failure. Its mechanism may include inducing oxidative stress and activating mitochondrial apoptosis pathway.