HSP22抑制线粒体功能障碍延缓糖尿病心肌病进展的机制研究

糖尿病心肌病（DCM）发病机制尚未完全阐明，线粒体功能障碍与DCM发生发展密切相关。热休克蛋白22（HSP22）可通过调节线粒体功能减轻细胞损伤。我们既往发现HSP22在2型糖尿病（T2D）小鼠心肌中表达下调，过表达HSP22减轻T2D小鼠心脏损害。进一步预实验观察到：高糖刺激损伤H9C2心肌细胞和下调HSP22表达，过表达HSP22基因减少心肌细胞损伤，同时减轻细胞线粒体功能障碍，提示HSP22可能通过抑制线粒体功能障碍延缓DCM进展。本课题拟上调和下调HSP22基因，构建小鼠DCM模型和高糖诱导心肌细胞损伤模型，从动物、细胞和分子水平，研究DCM进展过程中HSP22表达与线粒体功能障碍的关系；明确HSP22对DCM心肌细胞线粒体功能的影响并深入探讨相关分子机制。本项目将有助于阐明DCM的发病机制，为寻找防治DCM的新思路和新靶点奠定基础。

The pathogenesis of diabetic cardiomyopathy (DCM) has not been fully clarified. Studies have confirmed that mitochondrial dysfunction plays a key role in the development of DCM. Heat shock protein 22 (HSP22) alleviates cell damage by regulating mitochondrial function. Our previous study found that the expression of HSP22 was down-regulated in myocardium of type 2 diabetic (T2D) mice, overexpression of HSP22 improved cardiac function and mitochondrial dysfunction. Further pre-experiment observed that hyperglycemia induced H9C2 cardiomyocytes injury and decreased the expression of HSP22. Overexpression of HSP22 reduced cell damage and mitochondrial dysfunction in hyperglycemia-stimulated H9C2 cells. These results suggested that HSP22 may delay the progression of DCM by inhibiting mitochondrial dysfunction. In this study, up regulation and down regulation of HSP22 gene, construction of high glucose induced cardiomyocyte injury model and mouse DCM model will be used to examine the relationship between HSP22 expression and mitochondrial dysfunction, to elucidate the effect of HSP22 on mitochondrial function of DCM cardiomyocytes and its molecular mechanism. This study will contribute to the understanding of pathogenesis of DCM, and establish foundation to seek for new ideas and targets for the prevention and treatment of DCM.