清解化攻方对重症急性胰腺炎模型大鼠急性肺损伤的治疗作用及其机制  

The therapeutic effect of Qingjie Huagong decoction on acute lung injury in rats with severe acute pancreatitis model and its mechanism

作　　者：冯敏超 罗芳 唐曦平 李凯 朱晓东 张冰玉 陈国忠[4] FENG Min-chao;LUO Fang;TANG Xi-ping;LI Kai;ZHU Xiao-dong;ZHANG Bing-yu;CHEN Guo-zhong(the First Clinical Medical College,Guangxi University of Traditional Chinese Medicine,Nanning 530001,China;Guangxi Key Laboratory of Molecular Biology of Traditional Chinese Medicine and Preventive Medicine,Nanning 530001,China;Affiliated Cancer Hospital of Guangxi Medical University,Nanning 530001,China;the First Affiliated Hospital of Guangxi University of Traditional Chinese Medicine,Nanning 530001,China)

机构地区：[1]广西中医药大学第一临床医学院,广西南宁530001 [2]广西中医药防治医学分子生物重点实验室,广西南宁530001 [3]广西医科大学附属肿瘤医院,广西南宁5300013 [4]广西中医药大学第一附属医院,广西南宁530001

出　　处：《中国药理学通报》2024年第5期975-983,共9页Chinese Pharmacological Bulletin

基　　金：国家自然科学基金项目(No 82160890);广西自然科学基金面上项目(No 2020GXNSFAA297062);广西壮族自治区医疗卫生适宜技术开发与推广应用项目(No S2019021);广西中医药适宜技术开发与推广项目(No GZSY21-15);广西中医药大学研究生教育创新计划项目(No YCSW2023383);国家中医优势专科建设项目(No 2024010)。

摘　　要：目的使用网络药理学探究清解化攻方对重症急性胰腺炎(severe acute pancreatitis,SAP)相关急性肺损伤(acute lung injury,ALI)的可能作用机制,并通过动物实验验证。方法检索TCMSP、BATMAN-TCM、ETCM、SwissTargetPrediction数据库获取清解化攻方中各药物入血有效成分的作用靶点,在GeneCard数据库中检索获得SAP-ALI疾病靶点,将药物靶点与疾病靶点取交集获得共同靶点,随后通过STRING数据库及Cytoscape3.7.1软件对共同靶点进行蛋白互作网络分析,借助DAVID数据库行GO、KEGG富集分析,最后动物实验对关键信号通路予以验证。结果共筛选出清解化攻方治疗SAP-ALI有效活性成分28种,作用于42个共同靶点。PPI网络分析显示,STAT3、IL-6、TGFB1可能是核心靶点;GO、KEGG富集分析主要涉及细胞增殖、PI3K/AKT信号通路等。动物实验证实,清解化攻方能够改善SAP-ALI大鼠模型的胰腺、肺组织的病理情况,下调血清中α-淀粉酶、脂肪酶、IL-1β、IL-6、TNF-α表达水平,下调肺组织中PI3K/AKT1信号通路相关蛋白及mRNA表达水平。结论清解化攻方可能通过多成分、多靶点,多通路协同治疗SAP-ALI,其机制可能与抑制PI3K/AKT信号通路活化有关。Aim To investigate the possible mechanism of action of Qingjie Huagong decoction(QJHGD)on acute lung injury(ALI)associated with severe acute pancreatitis(SAP)using network pharmacology,and to verify it by animal experiments.Methods The TCMSP,BATMAN-TCM,ETCM,and SwissTargetPrediction databases were searched to obtain the action targets of the blood-entering active ingredients of each drug in the QJHGD.The GeneCard database was searched to obtain SAP-ALI disease targets.The drug targets and disease targets were intersected to obtain common targets.Subsequently,the common targets were analyzed by STRING database and Cytoscape 3.7.1 software for protein interaction network analysis.GO and KEGG enrichment analysis was performed with the help of DAVID database.Finally,the key signaling pathways were verified by animal experiments.Results A total of 28 active ingredients were screened out for the treatment of SAP-ALI with 42 common targets.PPI network analysis showed that STAT3,IL-6,and TGFB1 might be core targets;GO and KEGG enrichment analysis mainly involved cell proliferation,PI3K/AKT signaling pathways,etc.Animal experiments confirmed that QJHGD could improve the pathology of pancreas and lung tissues in SAP-ALI rat model,down-regulate the expression levels ofα-amylase,lipase,IL-1β,IL-6,and TNF-αin serum,and down-regulate the expression levels of proteins and mRNAs related to PI3K/AKT1 signaling pathway in lung tissues.Conclusion QJHGD synergistically treats SAP-ALI through multi-component,multi-target,and multi-pathway,with a mechanism that may be related to the inhibition of PI3K/AKT signaling pathway activation.

关 键 词：清解化攻方 PI3K/AKT1信号通路 重症急性胰腺炎相关急性肺损伤 网络药理学 实验验证 炎症反应 

分 类 号：R-332[医药卫生] R289.5R563.8R576.1