网膜素-1抑制ERK1/2磷酸化调控心肌去分化进程及机制研究

扩心病是一类原因不明的心肌病，预后差，且缺乏特异性治疗措施。目前认为心肌过度去分化是扩心病的重要病理机制。我们前期研究发现保护性脂肪因子Omentin-1-/-小鼠出生后7天时存在心肌过度去分化现象，同时ERK1/2磷酸化激活，而6月龄时出现扩心病样心肌改变；外源给予Omentin-1可以抑制损伤后心肌去分化。为此，我们提出Omentin-1通过抑制ERK1/2磷酸化激活从而抑制心肌去分化进程，参与扩心病发生发展。故本研究拟在细胞、动物水平进一步探讨Omentin-1抑制心肌细胞去分化、改善病理性心肌重构的作用及分子机制，为扩心病的药物研发提供新思路。

Dilated cardiomyopathy is a type of cardiomyopathy of unknown etiology with poor prognosis and lack of specific treatment measures. At present, cardiomyocyte dedifferentiation is an important pathological mechanism of dilated cardiomyopathy. Our previous study have found that Omentin-1 knockout mice (Omentin-1-/-) in postnatal 7 day exhibited excessive cardiomyocyte dedifferentiation and activation of ERK1/2 phosphorylation. While the heart of adult Omentin-1 -/- mice (6 months) was characterized by Cardiomyopathy-like myocardial changes. And Omentin-1 can inhibit cardiomyocyte dedifferentiation after injury. Based on previous findings, we propose that Omentin-1 inhibits cardiomyocyte dedifferentiation by inhibiting the activation of ERK1/2 phosphorylation and participates in the development of dilated cardiomyopathy. Therefore, this study intends to further explore the role of Omentin-1 in inhibiting the dedifferentiation of cardiomyocytes and improving the pathological ventricular remodeling in vivo and vitro, providing new ideas and intervention targets for the therapy of myocardial remodeling.