文献类型：期刊文献

中文题名：基于网络药理学及实验验证探究疏肝止泻方治疗腹泻型肠易激综合征作用机制

英文题名：Exploration on the Mechanism of Shugan Zhixie Prescription in Irritable Bowel Syndrome with Diarrhea Based on Network Pharmacology and Experimental Validation

作者：张金雪[1];刘俊宏[2];苏李宁[1];赖学倩[3];王丹[1];陈佳乐[1];陈雅洁[1];李红梅[1];李亚静[2]

第一作者：张金雪

机构：[1]甘肃中医药大学,甘肃兰州730000;[2]甘肃中医药大学附属医院,甘肃兰州730000;[3]甘肃省中心医院,甘肃兰州730000

第一机构：甘肃中医药大学

年份：2025

卷号：32

期号：12

起止页码：39

中文期刊名：中国中医药信息杂志

外文期刊名：Chinese Journal of Information on Traditional Chinese Medicine

基金：国家中医药管理局青年岐黄学者培养项目(2022年);甘肃省中医药科研课题重点项目(GZKZ-2021-6);甘肃省重点研发计划(22YFTFA100);甘肃省科学技术厅创新基地和人才计划(21JR7RA682);甘肃省省级重点人才项目和陇原青年创新创业人才项目(2022RCXM020);甘肃省卫生健康行业科研计划项目(GSWSQN2022-01)。

语种：中文

中文关键词：网络药理学;实验验证;疏肝止泻方;腹泻型肠易激综合征;TLR4/NF-κB通路

外文关键词：network pharmacology;experimental validation;Shugan Zhixie Prescription;irritable bowel syndrome with diarrhea;TLR4/NF-κB signaling pathway

摘要：目的 采用网络药理学探讨疏肝止泻方治疗腹泻型肠易激综合征(IBS-D)的作用机制,并进行体内实验验证。方法 利用TCMSP数据库筛选疏肝止泻方药物活性成分及潜在靶点,通过GeneCards、DisGeNET、OMIM数据库检索IBS-D靶点,将药物与疾病靶点取交集,利用STRING数据库构建蛋白相互作用网络,并进行GO和KEGG通路富集分析,以识别疏肝止泻方治疗IBS-D的关键信号通路。采用饥饱失常、束缚夹尾应激合并肠道灌注乙酸方法制备肝郁脾虚型IBS-D大鼠模型,并予疏肝止泻方低、中、高剂量干预14 d,ELISA检测大鼠血清二胺氧化酶(DAO)、白细胞介素(IL)-8、IL-18含量,Western blot、RT-qPCR分别检测结肠组织相关靶点蛋白及mRNA表达。结果 共获得疏肝止泻方药物活性成分26个、靶点553个,IBS-D疾病靶点1 930个,得到药物与疾病交集靶点184个,可能通过NF-κB、AGE-RAGE、Th17细胞分化等信号通路发挥治疗作用。动物实验结果表明,疏肝止泻方可有效减少模型大鼠排便次数,减少粪便含水量,抑制炎症因子释放,显著降低结肠组织TLR4、NF-κB蛋白表达(P<0.01),升高AQP3、AQP8、Occludin蛋白表达(P<0.01,P<0.05)。结论 疏肝止泻方可通过多途径、多靶点发挥治疗IBS-D作用,其机制可能与抑制TLR4/NF-κB信号通路及参与屏障修复有关。
Objective To investigate the mechanism of Shugan Zhixie Prescription in treating irritable bowel syndrome with diarrhea(IBS-D)using network pharmacology;To validate the findings through in vivo experiments.Methods Active components and potential targets of Shugan Zhixie Prescription were identified via the TCMSP database.Disease targets for IBS-D were retrieved from GeneCards,DisGeNET and OMIM databases.The intersection of drugs and disease targets was taken,and the protein interaction network was constructed by using STRING database.GO and KEGG pathways were enriched to identify the key signaling pathways of Shugan Zhixie Prescription in the treatment of IBS-D.The rat model of liver depression and spleen deficiency type IBS-D was established by the method of abnormal hunger and satiety,restraint pinch stress and intestinal perfusion of acetic acid.The rats were intervened with low-,medium-and high-dosage of Shugan Zhixie Prescription respectively for 14 days.Serum contents of diamine oxidase(DAO),interleukin(IL)-8,and IL-18 were measured by ELISA.Protein expressions and mRNA expressions of relevant targets in colonic tissue were detected using Western blot and RT-qPCR.Results A total of 26 active components and 553 targets of Shugan Zhixie Prescription were obtained,and 1930 targets of IBS-D disease were obtained,with 184 drug-disease intersection targets.The possible mechanism was related to NFκB,AGE-RAGE,Th17 cell differentiation and other signaling pathways.Animal experiments demonstrated that Shugan Zhixie Prescription could significantly reduce defecation frequency,fecal water content,and inflammatory cytokine levels in model rats.It markedly decreased TLR4 and NFκB protein expressions(P<0.01),while increased AQP3,AQP8 and Occludin protein expressions in colonic tissue(P<0.01,P<0.05).Conclusion Shugan Zhixie Prescription exerts therapeutic effects on IBS-D through multiple pathways and targets,and the mechanism may be related to inhibiting TLR4/NF-κB signaling pathway and promoting intestinal barrier repair.