心肌纤维化是多种心血管疾病的病理基础，其具体发病机制仍未完全阐明。蛋白质巯基亚硝基化修饰（SNO）参与多种心血管疾病的调节。预实验中发现磷酸葡萄糖异构酶（PGI/AMF）第403位半胱氨酸巯基亚硝基化修饰水平在心肌纤维化中明显增加，突变该位点可以抑制AngII诱导的成纤维细胞活化；AngII刺激下，iNOS表达增加，PGI/AMF酶活性降低，且与EGFR结合作用增强。我们拟在离体细胞及整体动物上，结合特异性半胱氨酸位点突变、基因敲除等方法验证科学假说：病理性刺激下，iNOS增加，促进PGI/AMF巯基亚硝基化修饰，1.SNO-PGI/AMF抑制PGI/AMF的酶活性，导致磷酸戊糖途径代谢增强，mTOR激活，2.SNO-PGI/AMF促进PGI/AMF与EGFR结合，激活ERK1/2共同促进心肌纤维化。研究可揭示影响心肌纤维化的新机制，为该疾病治疗提供新的分子干预靶点。

Cardiac fibrosis is the common pathological process of many cardiovascular diseases, and its underlying mechhanism has not been fully illuminated. S-nitrosylation plays an important role in many cardiovascular diseases. We discovered that PGI/AMF S-nitrosylation was increased during cardiac fibrosis, and mutation of Cysteine 403 inhibited Ang II-induced fibroblast activation. Under the stimulation of Ang II, the expression of iNOS increased, the activity of PGI/AMF decreased, and the binding with EGFR was enhanced. Thus, a scientific hypothesis was put forward: under pathological stimulation, iNOS increased, promoting PGI/AMF S-nitrosylation; 1. SNO-PGI /AMF inhibited the enzyme activity of PGI/AMF, leading to enhanced pentose phosphate pathway metabolism and mTOR activation; 2. SNO-PGI/AMF promoted PGI/AMF secretion, EGF receptor binding, and activated ERK1/2 to promote cardiac fibrosis. This project intends to test this hypothesis by combining specific cysteine site mutation and gene deletion in both isolated cells and mouse models. It is expected to reveal a new mechanism affecting cardiac fibrosis and provide a new molecular intervention target for the treatment of this disease.