基于网络药理学研究冬虫夏草治疗膜性肾病的作用机制

目的:基于网络药理学研究冬虫夏草治疗膜性肾病的潜在作用靶点及机制。方法:使用中药系统药理 学数据库和分析平台，筛选冬虫夏草的有效成分和靶点，通过GeneCards、OMIM、TTD、DrugBank、GAD等数据 库查找冬虫夏草治疗膜性肾病相关的靶点。利用 Cytoscape软件构建冬虫夏草作用靶点与有效成分之间的关系 网络，通过生物学信息注释数据库（DAVID）将冬虫夏草作用于膜性肾病的有效靶点基因进行GO富集分析和 KEGG通路分析。结果:根据口服利用度和药物相似性标准共筛选冬虫夏草的7个有效成分，39个可作用于膜性 肾病的作用靶点。关键靶点主要有细胞凋亡相关因子caspase3、丝裂原活化蛋白激酶（MAPK）、血管内皮生长 因子（VEGF）、一氧化氮合酶3 （NOS3）、过氧化物酶体增殖物活化受体γ（PPARγ）、c-Jun氨基末端激酶 （JNK）等，主要生物学过程包括磷脂转运蛋白活性、甾醇结合性、泛素蛋白连接酶结合性、类固醇激素受体 活性、信号调节活性等，关键信号通路主要涉及晚期糖基化终末产物（AGEs）-AGEs受体（RAGE）信号通路、 人类免疫缺陷病毒1型感染、人巨细胞病毒感染、VEGF信号通路等。结论:冬虫夏草可能主要通过抗炎、抗细 胞凋亡等发挥对膜性肾病的治疗作用。

Study on the mechanism of Cordyceps sinensis in treating membranous nephropathy based on network pharmacology

Objective: To study the potential target and mechanism of Cordyceps sinensis for membranous nephropathy（MN） based on network pharmacology. Methods: The pharmacological database and analysis platform of Chinese medicine system were used to screen the active components and targets of Cordyceps sinensis, and the targets related to Cordyceps sinensis treatment of membranous nephropathy were found through GeneCards，OMIM，TTD，DrugBank，GAD and other databases.Cytoscape software was used to construct the relationship network between the target of Cordyceps sinensis and the active ingredients，and the target gene of Cordyceps sinensis acting on membranous nephropathy was analyzed by GO enrichment and KEGG pathway analysis through the biological information annotation database（DAVID）. Results: A total of 7 active ingredients of Cordyceps sinensis were screened according to the oral availability and drug similarity criteria，and 39 targets that could act on MN. The key targets were caspase3， mitogen-activated protein kinase（MAPK），vascular endothelial growth factor（VEGF），nitric oxide synthase 3（NOS3），and peroxidase proliferative activated receptor（PPAR）γ，c-Jun N- terminal kinase（JNK），etc. The main biological processes included phospholipid transporter activity，sterol binding，ubiquitin protein ligase binding，steroid hormone receptor activity， signal regulation activity，etc. The key signaling pathways mainly involved AGEs-RAGE signaling pathway，human immunodeficiency virus type 1 infection，human cytomegalovirus infection，and VEGF signaling pathway. Conclusion: Cordyceps may exert its therapeutic effect on MN mainly through anti-inflammatory and anti-apoptosis.