缝隙连接重构导致的电生理基质异常是心梗后心源性猝死的重要原因。前一个基金发现稳心颗粒能减轻miR-1对缝隙连接蛋白的合成抑制，但对其降解的影响不明。内质网应激未折叠蛋白反应（UPR）-内质网相关降解（ERAD）级联是调节蛋白降解的必经通路，其如何影响心肌缝隙连接重构的病理机制目前是研究盲点。项目假说：内质网应激UPR-ERAD级联是调控心梗后缝隙连接重构的机制之一，稳心颗粒能干预这一级联改善缝隙连接重构。本项目拟建立心梗大鼠模型，研究UPR-ERAD级联的启动、调节、执行机制及其与缝隙连接重构的相关性；细胞实验借助UPR-ERAD特异性激动或阻滞剂，验证UPR-ERAD级联过度激活或抑制条件下引起缝隙连接降解的具体途径及稳心颗粒的作用。如假说成立，将与前一个基金相辅相成，较完整的阐述心梗后缝隙连接蛋白合成和降解稳态失衡的分子机制，同时也为心梗后心律失常的防治提供一个新靶点和可供选择的中药。

The abnormal electrophysiological substrate induced by gap junction remodeling is an important cause of sudden cardiac death after myocardial infarction. Our previous National Natural Science Fund program found that wenxin granule can reduce the inhibition of connexins synthesis induced by miR-1. But there is no research on connexins degradation aspect in this program. Endoplasmic reticulum stress the unfolded protein response (UPR) - endoplasmic reticulum associated degradation (ERAD) cascade is a necessary pathway in regulation of protein degradation. But how does it affect myocardial gap junction remodeling is the research blind spot. The hypothesis of current program is that endoplasmic reticulum stress UPR-ERAD cascade is one of the mechanisms to regulate gap junction remodeling after myocardial infarction, and wenxin granule can intervene in this cascade to protect the gap junction. Current program will establish a rat model of myocardial infarction, and will study the initiation, regulation and execution mechanism of UPR-ERAD cascade, further will study the relationship between UPR-ERAD cascade and gap junction remodeling; Cell experiment will verify the specific ways of connexins degradation and effects of wenxin granule under conditions of excessive activation or inhibition by use of UPR-ERAD specific agonists or antagonists. If the current hypothesis is true, a relatively complete molecular mechanism of the synthesis and degradation of connexins will be described through the current and the previous programs which complement each other. At the same time, the current program also provides a new target and a potential alternative and complementary traditional Chinese medicine for the prevention and treatment of arrhythmia after myocardial infarction.