肾病综合征（NS）是一种严重威胁人类健康的慢性肾脏疾病，糖皮质激素等免疫抑制剂存在毒副作用难以在临床推广。加快研发高效低毒的新型肾病药物已刻不容缓。TRPC6抑制剂是治疗NS药物研发的新方向。前期研究我们发现冬虫夏草菌次级代谢产物具有抑制TRPC6过表达活性，并首次在冬虫夏草菌中发现萜类活性成分，且利用中药网络药理学分析方法发现冬虫夏草菌治疗肾病综合征的主要活性分子机制是调控肌动蛋白重组/迁移相关信号通路；大量基础研究和临床试验报道了冬虫夏草菌具有治疗肾病药效，但活性成分和药效分子机制还不明确。本项目拟在前期研究基础上，结合表观遗传学调控技术，挖掘冬虫夏草菌中具有TRPC6抑制活性的萜类等天然产物，并采用分子对接设计进行结构优化，利用TRPC6过表达的细胞模型和动物体内活性测试等方法筛选出活性显著、作用机制明确的TRPC6抑制剂候选药物，为研发具有自主知识产权的TRPC6抑制剂建立基础。

Nephrotic syndrome is a kind of chronic kidney disease, which seriously threatens human health, glucocorticoids and other immunosuppressive drugs have different degrees of side effects, which make it difficult to promote them in clinical practice, so, it is necessary to speed up the development of new therapeutic drugs with high efficiency and low toxicity. The research and development of TRPC6 inhibitors is a new direction for the treatment of nephrotic syndrome。In the previous study, we found that the secondary metabolites of the Cordyceps mycelium had the activity of inhibiting TRPC6 overexpression, and terpenoids were found in Cordyceps mycelium for the first time. From the study of the Chinese medicine network pharmacology, it was found that the main active molecular mechanism of Cordyceps sinensis in the treatment of nephrotic syndrome was the regulation of actin recombination/migration related signal pathway. A large number of basic research and clinical trials have reported that Cordyceps mycelium has therapeutic effect on kidney disease, but the active ingredients and molecular mechanism are not clear. In this project, on the basis of previous research and in combination with epigenetic regulation technology, natural products such as terpenes with TRPC6 inhibitory activity in Cordyceps mycelium will be excavated, and molecular docking design will be used to optimize the structure of the lead compounds. Through cell model of TRPC6 overexpression and animal activity test, candidate drugs with significant activity and clear active mechanism will be screened out for research, and to establish the basis for the research and development of TRPC6 inhibitors with independent intellectual property rights.