健脾化瘀法防治慢性萎缩性胃炎“炎-癌”转化的系统评价及网络药理学研究  

Systematic Evaluation and Network Pharmacology Research of Jianpi Huayu Method for the Prevention and Treatment of the Inflammatory-Carcinoma Transformation in Chronic Atrophic Gastritis

作　　者：倪家慧 钟日升[2] 王雄文[3] 周恒立 刘昌华 田雯 潘华峰[1,4] NI Jiahui;ZHONG Risheng;WANG Xiongwen;ZHOU Hengli;LIU Changhua;TIAN Wen;PAN Huafeng(Guangzhou University of Chinese medicine,Guangzhou 510405 Guangdong,China;Guangdong University of Foreign Studies,Guangzhou 510006 Guangdong,China;The First Affiliated Hospital of Guangzhou University of Chinese Medicine,Guangzhou 510405 Guangdong,China;Jiangsu Provincial Collaborative Innovation Center of TCM Cancer Prevention,Nanjing 210023 Jiangsu,China)

机构地区：[1]广州中医药大学,广东广州510405 [2]广东外语外贸大学,广东广州510006 [3]广州中医药大学第一附属医院,广东广州510405 [4]江苏省中医药防治肿瘤协同创新中心,江苏南京210023

出　　处：《中药新药与临床药理》2023年第7期997-1009,共13页Traditional Chinese Drug Research and Clinical Pharmacology

基　　金：广东省重点领域研发计划项目(2020B1111100011);国家中医药管理局中医药创新团队及人才支持计划项目(ZYYCXTD-C-202208);广州中医药大学“双一流”与高水平大学学科协同创新团队项目(2021XK36);国家自然科学基金项目(81973816);广东省中医药局科研项目(20215005)。

摘　　要：目的系统评价健脾化瘀法治疗慢性萎缩性胃炎(CAG)、胃癌前病变(GPL)的临床有效性及安全性;同时运用网络药理学预测国医大师周岱翰教授健脾化瘀法验方理中消痞方防治胃“炎-癌”转化的效应物质基础和分子机制。方法检索中国知网(CNKI)、万方数据库(Wangfang)、维普中文期刊(VIP)、中国生物医学文献数据库(SinoMed)、PubMed、Embase、Cochrane Library、Web of Science等数据库,筛选各数据库建库至2023年3月关于健脾化瘀法治疗CAG、GPL的随机对照临床试验,采用RevMan 5.4进行系统评价,利用Stata 17.0软件进行Egger检测评估发表偏倚;运用TCMSP、TCMIP及GeneCards等数据库挖掘理中消痞方的主要活性成分,筛选CAG、GPL的疾病靶点;应用Cytoscape软件构建药物-活性成分-靶点互作网络;String平台构建共同靶点蛋白互作网络(PPI);应用Metascape数据库对共同靶点进行基因本体(GO)功能分析和京都基因与基因组百科全书(KEGG)通路富集分析;运用Autoduck Vina软件对理中消痞方的活性成分与核心靶点进行验证。结果共纳入13篇文献,涉及1510例患者。Meta分析结果提示,与西医常规治疗相比,健脾化瘀法可显著提高CAG、GPL患者临床疗效[RR=1.22,95%CI(1.16,1.29),P<0.00001]、胃镜疗效[RR=1.49,95%CI(1.10,2.01),P=0.010]及病理疗效[RR=1.33,95%CI(1.06,1.66),P=0.01],改善CAG、GPL患者胃黏膜萎缩[RR=1.42,95%CI(1.31,1.54),P<0.00001]、肠上皮化生[RR=1.84,95%CI(1.42,2.38),P<0.00001]、异型增生[RR=2.87,95%CI(1.31,6.24),P=0.008],且安全性较好。纳入文献不存在发表偏倚;网络药理学结果提示,理中消痞方10味中药包含活性成分189个,治疗CAG、GPL的潜在作用靶点128个,涉及的核心成分有槲皮素、山奈酚、β-谷甾醇和豆甾醇等,核心作用靶点为JUN、TP53、HSP90AA1、MAPK3、MAPK1、MYC、MAPK13;GO功能富集共筛出生物学过程1143条、细胞组成39条、分子功能105条,交集靶点主要涉及受体�Objective To systematically evaluate the clinical efficacy and safety of Jianpi Huayu method in the treatment of chronic atrophic gastritis(CAG)and gastric precancerous lesions(GPL),as well as to predict the material basis and molecular mechanism of Lizhong Xiaopi Formula(LZXP)proposed by Professor ZHOU Daihan based on Jianpi Huayu Method in the prevention and treatment of gastric“inflammation-carcinoma”transformation via network pharmacology.Methods Randomized controlled trials of Jianpi Huayu Method in the treatment of CAG and GPL were searched from CNKI,Wangfang,VIP,SinoMed,PubMed,Embase,Cochrane Library,Web of Science.The retrieval time was from database inception to March 2023.RevMan 5.4 was used for systematic evaluation,while Egger detection was used for evaluating publication bias by Stata 17.0.The TCMSP database,TCMID database and GeneCards database were used to collect the potential active ingredients of LZXP as well as the disease targets of CAG and GPL.Cytoscape software was used to construct the drug-active ingredient-target interaction network.The protein-protein interaction(PPI)network was constructed by using String database.The common targets were enriched by gene ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analysis.Molecular docking of active ingredients and core targets of LZXP was performed using Autodock Vina software.Results Thirteen clinical studies were included in this study,involving a total of 1510 patients.The results of Meta-analysis showed that,compared with western routine treatment,Jianpi Huayu Method can significantly improve the clinical effect[RR=1.22,95%CI(1.16,1.29),P<0.00001],the clinical effect of gastroscopy[RR=1.49,95%CI(1.10,2.01),P=0.010],pathological effect[RR=1.33,95%CI(1.06,1.66),P=0.01],gastric atrophy[RR=1.42,95%CI(1.31,1.54),P<0.00001],intestinal metaplasia[RR=1.84,95%CI(1.42,2.38),P<0.00001]and dysplasia[RR=2.87,95%CI(1.31,6.24),P=0.008]of CAG and GPL patients,which showed great safety in the clinic.There was no publication bias in the

关 键 词：慢性萎缩性胃炎 胃癌前病变 健脾化瘀法 理中消痞方 系统评价 网络药理学 

分 类 号：R285.5[医药卫生—中药学]