中文摘要：

目的探讨葡萄糖＂糖酵解-有氧氧化脱耦联＂在慢性心肌肥厚进展过程中的作用及其机制。方法采用小鼠主动脉缩窄（TAC）模型诱导慢性心肌肥厚至慢性心力衰竭过程。采用Western blotting检测慢性心力衰竭进展过程中磷酸化丙酮酸脱氢酶（p-PDH）蛋白的动态表达变化,同时观察DCA药物处理对小鼠心功能及生存曲线的影响;采用TUNEL法原位检测两组心肌细胞凋亡的改变。结果 Western blotting结果表明,小鼠TAC模型中p-PDH的表达在术后第1天即开始升高,术后第3天达到峰值,术后2周仍升高,而在术后12周时表达很低。与对照组相比,DCA处理组的p-PDH明显降低（P〈0.05）;进一步超声心功能分析表明,DCA处理组加速了失代偿期心功能的恶化,进而降低了小鼠的20周生存率;TUNEL法半定量分析结果显示,DCA处理组的心肌细胞凋亡指数（29.3±2.5）明显高于对照组（18.8±1.9,P〈0.05）。结论心肌的葡萄糖代谢从糖酵解向氧化磷酸化转变促进了代偿性心肌肥厚向失代偿性心力衰竭的转变;葡萄糖氧化磷酸化促进心力衰竭的机制与心肌细胞凋亡增多有关。

英文摘要：

Objective To investigate the role of ＂glycolysis-uncoupling of glucose oxidation＂ in the development of chronic cardiac hypertrophy and its mechanism.Methods Mouse transaortic-constriction（TAC） model was reproduced to mimic the process of chronic cardiac hypertrophy and development of heart failure.The dynamic expression of phosphorylated pyruvate dehydrogenase（p-PDH） during the progression of chronic cardiac heart failure was analyzed by Western blotting.Then the effect of dichloroacetate（DCA）-treatment on cardiac function and survival was evaluated.At the same time the cardiocyte apoptosis was compared between the two groups.Results The p-PDH levels were elevated 1 day after TAC,peaking on the 3rd day,and continued to be elevated 14 days after TAC,then significantly lowered 12 weeks after TAC.Compared with control group,the p-PDH expression was significantly down-regulated in DCA-treatment group（P＆lt;0.05）.Echocardiography showed that DCA-treatment during TAC contributed to the dysfunction of chronic cardiac hypertrophy.TUNEL analysis showed that the apoptotic index in the DCA-treatment group（29.3±2.5） was significantly higher than that in control group（18.8±1.9,P＆lt;0.05）.Conclusions Enforced coupling between cytosolic glycolysis and mitochondrial oxidative phosphorylation via DCA acutely contributes to the dysfunction of chronic cardiac hypertrophy in pressure-overloaded heart.he mechanism is possibly associated with an increase in cardiocyte apoptosis.