中医药治疗慢性萎缩性胃炎的多途径作用机制

Traditional Chinese Medicine Treats Chronic Atrophic Gastritis via Multiple Pathways

目的:基于数据挖掘、系统药理学、分子对接系列研究方法,针对中医药治疗慢性萎缩性胃炎(CAG)的有效专利复方进行用药规律挖掘,进而预测不同功效中药治疗CAG的潜在作用靶标及分子机制。方法:通过国家知识产权局中国专利系统提取干预CAG的中药复方,综合文献利用中药系统药理学数据库与分析平台(TCMSP)、中医药综合数据库(TCMID)、UniProt数据库获取重点功效药物有效成分与靶点;基于GeneCards、DisGeNet、在线人类孟德尔遗传数据库(OMIM)、MalaCards、京都基因与基因组百科全书(KEGG)、Reactome数据库获取CAG潜在靶点与通路,通过R Studio 4.1.2实现基因本体论(GO)注释和KEGG富集分析;基于STRING 11.0数据库构建蛋白质-蛋白质相互作用网络(PPI);采用分子对接软件AutoDock Vina 4.2.6对关键靶点和成分进行对接验证。结果:提取治疗CAG复方228个,分析用药规律,药性多温、寒,药味多苦、甘,归经多脾、胃、肝;补气药、理气药、清热药、活血药、补血药为重点功效药物。对比不同功效药物对应靶点与CAG靶点,发现中药治疗CAG的机制与p53信号通路、丝裂原活化蛋白激酶(MAPK)信号通路、磷脂酰肌醇3-激酶/蛋白激酶B(PI3K/Akt)信号通路、叉头转录因子O(FoxO)信号通路、血管内皮生长因子(VEGF)信号通路、低氧诱导因子-1(HIF-1)信号通路等相关,分子对接结果证实中药成分与关键受体蛋白具有对接活性。结论:研究初步分析了中药治疗CAG的配伍规律,提示补气药、理气药、清热药、活血药、补血药分别从调控细胞增殖与凋亡、调节氧化应激、防御致癌物质、促进胃酸分泌,改善局部微循环等多方面组成了多靶点、多途径、多环节治疗CAG的作用机制网络,为CAG的中药治疗提供了有益探索。

Objective:To mine the compatibility rules of patented traditional Chinese medicine(TCM) compound prescriptions for treating chronic atrophic gastritis(CAG) by systems pharmacology and molecular docking methods,and predict the targets and molecular mechanisms of Chinese medicinals with different efficacy in the treatment of CAG.Method:The TCM compound prescriptions for treating CAG were extracted from the patent system of the China National Intellectual Property Administration.The active components and targets of the prescriptions were retrieved from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP),Traditional Chinese Medicine Integrative Database(TCMID),and UniProt.The candidate targets and pathways of CAG were obtained from GeneCards,DisGeNet,Online Mendelian Inheritance in Man(OMIM),MalaCards,Kyoto Encyclopedia of Genes and Genomes(KEGG) and Reactome.The gene ontology(GO) functional annotation and KEGG pathway enrichment were realized by R Studio 4.1.2.STRING11.0 was employed to build the protein-protein interaction(PPI) network,and AutoDock Vina 4.2.6 was used for the docking between key targets and components.Result:A total of 228 TCM compound prescriptions for treating CAG were extracted.The medicinals used in these prescriptions mainly had warm or cold nature,bitter or sweet taste,tropism to the spleen,stomach,and liver meridians,and the efficacy of tonifying Qi,regulating Qi movement,clearing heat,and activating and toniying blood.The prescriptions mainly treated CAG via p53,mitogen-activated protein kinase(MAPK),phosphatidylinositol 3-kinase(PI3K)/protein kinase B(Akt),forkhead box protein O(FoxO),vascular endothelial growth factor(VEGF),and hypoxia-inducible factor-1(HIF-1) signaling pathways.Molecular docking results confirmed that the active components in the prescriptions had docking activities with key receptor proteins.Conclusion:This study preliminarily analyzed the compatibility rules of TCM compound prescriptions in the treatment of CAG.The medicinals with different efficacy treat CAG by regulating cell proliferation,apoptosis,and oxidative stress response,preventing carcinogen production,promoting gastric acid secretion,and improving local microcirculation in a multi-target,multi-pathway,multilink manner.The findings facilitate the research on the TCM treatment of CAG.