缺血再灌注心律失常是缺血性心脏病患者心脏性猝死的重要原因。有证据表明瞬时受体电位M4(TRPM4)可能在缺血再灌注心律失常中发挥重要作用,然而具体机制尚未阐明。近来发现磺酰脲受体1(SUR1)在神经组织具有调控TRPM4的作用。我们预实验发现心肌细胞在缺氧时TRPM4表达升高，复氧时表达量则没有进一步升高，而SUR1则随缺氧复氧时间的延长表达均呈增加趋势。据此我们推测TRPM4通道可能在转录后受SUR1调控参与心肌缺血再灌注心律失常。本项目拟采用在体大鼠心脏缺血再灌注损伤动物模型,研究SUR1对TRPM4的调控作用，以及对缺血再灌注心律失常的影响;探讨SUR1调控TRPM4的可能机制,分析SUR1对TRPM4的转录后SUMO化修饰的影响。本研究将有助于阐明TRPM4在缺血再灌注心律失常中的作用及其分子机制, 为探寻新的防治靶点提供线索。

Ischemia-reperfusion arrhythmia is one of main causes of sudden cardiac death in ischemic heart diseases. Recent evidences suggest that Transient Receptor Potential Melastatin 4(TRPM4) plays important role in ischemia-reperfusion arrhythmia, but its mechanism is still not well established. Sulfonylurea receptor 1(SUR1) was reported to regulate TRPM4 in nerves tissues. .Our previous studies revealed that the expression of TRPM4 in H9C2 cells were elevated in hypoxia conditions, but were not elevated further in reoxygenation conditions, and there was an increased expression of SUR1 in hypoxia/ reoxygenation process. We hypothesized that TRPM4 was regulated by SUR1 post-transcriptionally and influence ischemic-reperfusion arrhythmia. We aims to investigate the influence of SUR1 to TRPM4 and the arrhythmia in acute myocardial ischemia-reperfusion rat model; then, we analyze the exact regulatory mechanism of SUR1 at the cellular level, and its effect on SUMOlyzation of TRPM4 post-transcrptionally. This study will help to clarify the role of SUR1 and TRPM4 in myocardial ischemia-reperfusion arrhythmia, provide new clue for further therapy and prevention of ischemia-reperfusion arrhythmia.