前肾素受体参与心肌细胞焦亡及影响中性粒细胞的NETosis对糖尿病心肌病心肌损伤的影响及意义

糖尿病心肌病（DCM）的心肌损伤是当今研究的热点与难点问题。目前认为肾素血管紧张素系统的新成员-前肾素受体(PRR)可以通过多种机制参与DCM的病理过程。近年来的研究发现心肌细胞焦亡与中性粒细胞的NETosis促进了心肌损伤的病理过程。我们前期的研究发现在DCM中，PRR基因过表达鼠心肌焦亡及中性粒细胞NETosis明显增加，提示PRR促进了心肌细胞焦亡及中性粒细胞NETosis的病理过程。我们提出假说：PRR参与焦亡及调控“焦亡-NETs”这一环路在DCM的病理过程中起重要作用。为了阐明PRR调控“焦亡-NETs”这一环路在DCM病理机制中的作用，本研究构建PRR基因过表达鼠、PRR基因沉默鼠，并进行体外细胞实验。本课题试图阐明PRR调控“焦亡-NETs”这一环路在DCM病理机制中的作用，探讨PRR调控“焦亡-NETs”引起心肌损伤的分子机制,为DCM心肌损伤的治疗提供新的靶点。

The myocardial injury of diabetic cardiomyopathy (DCM) is a hot and difficult problem in the present research. Currently,(Pro)renin receptor (PRR)，as a new member of renin-angiotensin system (RAS), is believed to be involved in the pathological process of DCM through a variety of signaling pathways and mechanisms. In recent years, studies have found that both cardiomyocyte pyroptosis and neutrophils NETosis can promote myocardial injury. At present, there are few researches on whether PRR is involved in the process of cardiomyocyte pyroptosis and neutrophil NETosis in DCM. Our previous primary study found that the cardiomyocyte pyroptosis and neutrophil NETosis are significantly higher in DCM of PRR knock-in mice than that of wild-type mice, the result indicated PRR overexpression takes part in the pathogenesis of cardiomyocyte pyroptosis and neutrophil NETosis. In this study, we test the hypothesis that PRR may promote cardiomyocyte pyroptosis and neutrophil NETosis in DCM, take part in the interaction between myocardial pyroptosis and neutrophil NETosis. In vivo study,the PRR knock-in and PRR gene silencing mice were used to evaluate the effects of PRR on regulating pyroptosis and NETs in DCM. In vitro study, cardiomyocyte culture from PRR knock-in mice was performed to assess the effects of PRR on the pathogenesis of myocardial proptosis and neutrophil NETosis and its interactions. This study wants to explore the effect and mechanism of PRR regulating the loop of “pyroptosis-NETs” in the pathogenesis of DCM, and provide a new target for treatment of DCM.