阐明心肌肥厚向心衰转化的机制对心衰防治具有重要意义。心肌线粒体氧化磷酸化功能减弱诱发心衰,机制未明;信号转导和转录活化因子-3 (STAT3)具有抗心衰作用,心衰时其蛋白水平和活性下降,下降机制未明.我们前期通过线粒体解耦联剂和线粒体呼吸复合体I抑制剂抑制心肌线粒体氧化磷酸化,发现抑制心肌线粒体氧化磷酸化可显著降低STAT3的表达和活性,因此提出假设:心衰时STAT3信号下降源自心肌线粒体氧化磷酸化功能减弱,且线粒体氧化磷酸化功能减弱通过抑制STAT3促使心肌肥厚向心衰转化.本课题拟研究:(1)心肌线粒体氧化磷酸化功能减弱抑制STAT3信号的作用及机制,包括对STAT3表达和活性的影响及机制;(2)心肌线粒体氧化磷酸化功能减弱抑制STAT3信号促使心肌肥厚向心衰转化。本课题将阐明心衰时STAT3信号下降的原因，并提出心肌线粒体氧化磷酸化功能减弱抑制STAT3信号是心衰转化的新机制。

It is important to clarify the mechanisms of the transition from heart hypertrophy to heart failure. Impairment of cardiac mitochondrial oxidative phosphorylation induces heart failure, the mechanism by which is unclear; STAT3 has the protective effects against heart failure. The expression and activity of STAT3 decrease in heart failure, the mechanism by which remains unelucidated. Our preliminary study found that inhibition of myocardial mitochondrial oxidative phosphorylation by mitochondrial chemical uncouplers and mitochondrial respiratory chain complex I inhibitor significantly inhibited the activity and protein level of STAT3. Therefore, we put forward the project that STAT3 signaling inhibition in heart failure might be due to the impairment of myocardial mitochondrial oxidative phosphorylation, and the impairment of myocardial mitochondrial oxidative phosphorylation induces the heart failure transition through inhibiting STAT3 signaling. The project will study: (1) the effects and mechanisms of the inhibition of STAT3 signaling (including the inhibition of STAT3 activity and total STAT3 protein level) by the impairment of myocardial mitochondrial oxidative phosphorylation; (2) the inhibition of STAT3 signaling by the impairment of myocardial mitochondrial oxidative phosphorylation contributes to the transition from heart hypertrophy to heart failure. The project will elucidate the reason of the inhibition of STAT3 signaling in heart failure, and puts forward the novel mechanism of the transition to heart failure that the impairment of myocardial mitochondrial oxidative phosphorylation inhibits STAT3 signaling.