IP6K1调控脂联素的分子机制及其在心肌缺血再灌注损伤过程中作用的研究

六磷酸肌醇激酶1（inositol hexakisphosphate kinase 1，IP6K1）及其主要产物5-InsP7对多种细胞生物学功能起着关键的调控作用。我们发现敲除IP6K1显著减少缺血再灌注导致的心肌梗死面积。这一发现提示IP6K1可能是治疗心肌梗死的新靶点。随后我们发现IP6K1结合脂联素，敲除IP6K1显著增加脂联素的蛋白水平。脂联素是心肌细胞的重要保护因子。因此，敲除IP6K1保护缺血心肌细胞的分子机制可能是其促进了脂联素的表达分泌。本项目中，我们将重点研究心肌缺血再灌注损伤过程中IP6K1对脂联素的调控作用及其分子机制，并探讨以IP6K1为分子靶点治疗心肌梗死的可行性。研究结果将为治疗心肌梗死提供新的策略和实验依据。

Inositol hexakisphosphate kinase-1 (IP6K1) and its major product 5-diphosphoinositol pentakisphosphate (5-InsP7) mediate diverse biological functions. We find that deletion of IP6K1 substantially reduces myocardial infarct size in an ischemia-reperfusion animal model, indicating IP6K1 may be a novel therapeutic target for myocardial infarction. Mechanistically, we find that IP6K1 associates with adiponectin. Deletion of IP6K1 dramatically increases adiponectin protein levels. Adiponectin mitigates myocardial infarction. Thus knocking out IP6K1 may protect cardiomyocytes from ischemia-reperfusion injury via raising adiponectin. In this project, we will validate the efficacy of IP6K1 as a target for treating myocardial infarction and study the mechanism by which IP6K1 regulates adiponectin and its implication in myocardial ischemia-reperfusion injury.