糖尿病的心血管并发症已成为糖尿病患者死亡的主要原因，其主要发病机制是高血糖激活了以ROS为核心的RAAS、内质网应激、炎性反应等网络介导的心肌及血管内皮细胞损伤。如何阻断该过程是降低心血管疾病并发症的重要手段。研究发现，ROS等损伤性因素的出现伴有容积敏感性（VSOR）氯离子通道的激活，阻断该通道能有效挽救受损的细胞，那么VSOR氯离子通道是否也参与了高糖诱导心肌损伤的发病过程？其机制如何？目前国内外尚未见报道。本课题拟在高糖诱导心肌细胞损伤模型上，一方面观察高糖刺激对心肌细胞膜VSOR氯通道的影响；另一方面，通过激活或阻断剂阻断VSOR氯通道，观察VSOR氯通道功能变化对高糖诱导心肌损伤的作用，以及核心信号分子ROS与内质网应激、炎性因子、细胞凋亡等指标及信号通路的调节。首次探讨高糖介导的心肌细胞损伤中氯离子通道的调控作用及分子机制，为预防和治疗糖尿病心肌病提供全新的依据和策略。

Cardiovascular complications of diabetes have become the main cause of death. The main pathogenesis is that hyperglycemia-induced by diabetes activates RAAS system, the production of ROS, endoplasmic reticulum stress and inflammatory responses, which lead to the injury of cardiomyocytes and vascular endothelial cells. If these processes could be inhibited, cardiovascular complications may be alleviated. It has been reported that these factors above activate VSOR chloride channel, whereas inhibiting this channel could rescue injured cardiomyocytes. Does VSOR chloride channel also participate in the process of cardiomyocyte injury induced by diabetes? If so, what is the mechanism? So far, it has not been reported. To elucidate this hypothesis, high glucose is going to be used to establish cardiomyocyte injury model in this study. First, we will investigate the influence of high glucose to the VSOR chloride channels of cardiomyocyte. Next, VSOR chloride channel function will be changed by activating or inhibiting VSOR chloride channel. With this prerequisite, the cell injury induced by high glucose would be detected. In addition, biochemical and signal pathways including ROS, endoplasmic reticulum stress, apoptosis, inflammatory responses would aslo be tested. In this topic, we will study the regulation and mechanism of VSOR chloride channel and cardiomyocyte injury induced by high glucose for the first time. Moreover, we may provide new evidence and strategy to the prevention and treatment of diabetic cardiomyopathy