芪黄通秘软胶囊治疗功能性便秘的作用机制研究  

Mechanism of Qihuang Tongmi(芪黄通秘)Soft Capsules in the Treatment of Functional Constipation

作　　者：张秋艳 任钧国 宋国超[2] 李振江 姜云耀 ZHANG Qiuyan;REN Junguo;SONG Guochao;LI Zhenjang;JIANG Yunyao(College of Clinical Medicine,Beijing University of Chinese Medicine,Bejing100029;School of Pharmaceutical Sciences,Tsinghua University,Beijing 100084;Hebei Provincial Key Laboratory of Quality Process Control of Classical Formulas and Modern Chinese Medicines,Shijiazhuang 051430;Key Laboratory of Chinese Medicine Pharmacology and State Key Laboratory of Natural Medicines,Institute of Basic Medicine,Xiyuan Hospital of China Academy of Chinese Medical Sciences,Beijing 100091)

机构地区：[1]北京中医药大学临床医学院,北京100029 [2]清华大学药学院,北京100084 [3]河北省经典名方与现代中药质量过程控制重点实验室,石家庄051430 [4]中国中医科学院西苑医院、基础医学研究所、中药药理北京市重点实验室,北京100091

出　　处：《中药药理与临床》2025年第2期21-26,共6页Pharmacology and Clinics of Chinese Materia Medica

摘　　要：目的:探索芪黄通秘软胶囊治疗功能性便秘(functional constipation,FC)的作用机制。方法:通过网络药理学预测芪黄通秘软胶囊治疗FC的药效成分、靶点基因及相关通路,根据文献对预测信号通路进行筛选,分子对接预测活性成分与通路靶点的亲和力。将小鼠随机分为正常对照组、模型对照组、芪黄通秘软胶囊0.5、1 g/kg组,造模成功后各组灌胃给予相应药物或生理盐水,观察芪黄通秘软胶囊对FC小鼠粪便质量和含水率、小肠推进率的影响;采用ELISA法检测小鼠血浆中胃泌素(GAS)及胃动素(MTL)的含量;通过Western blot法验证通路靶点的蛋白表达。结果:通过网络药理学及文献调研发现芪黄通秘软胶囊中78个活性成分通过73个作用靶点调控PI3K-AKT、mTOR、MAPK和IL-17等8条信号通路发挥治疗FC的作用,主要涉及细胞凋亡、基因的表达调控等生物过程;分子对接结果显示,槲皮素、木犀草素、大黄酚等活性成分与PIK3CG、AKT1均有较高的亲和力。动物实验结果表明,与正常对照组比较,模型对照组小鼠粪便质量、含水率及小肠推进率明显降低(P<0.05或P<0.01),结肠组织中p-PI3K、p-AKT、PI3K、AKT的蛋白表达显著下调(P<0.01);与模型对照组比较,芪黄通秘软胶囊各组小鼠粪便质量、含水率及小肠推进率明显增加(P<0.05或P<0.01),芪黄通秘软胶囊1.0 g/kg组小鼠血浆中GAS、MTL的含量显著增加(P<0.01),结肠组织中p-PI3K、p-AKT、PI3K、AKT的蛋白表达明显上调(P<0.05或P<0.01)。结论:芪黄通秘软胶囊可能通过调控PI3K-AKT信号通路,升高GAS、MTL的含量,调节肠道运动从而发挥治疗FC的作用。Objective:To explore the mechanism of Qihuang Tongmi(芪黄通秘)Soft Capsules(QTSC)in the treatment of functional constipation(FC).Methods:Network pharmacology was utilized to predict the active components,target genes,and related pathways of QTSC in treating FC.Based on the literature,the predicted signaling pathways were screened,and molecular docking was performed to predict the binding affin-ity between active components and pathway targets.Mice were randomly divided into a normal control group,a model control group,and QTSC groups at doses of 0.5 g/kg and 1.0 g/kg.After successful modeling,each group was administered the corresponding drug or saline via ga-vage.The effects of QTSC on fecal weight,water content,and small intestinal propulsion rate in FC mice were observed.Plasma levels of gas-trin(GAS)and motilin(MTL)were measured using ELISA,and protein expression of pathway targets was verified by Western blotting.Results:Network pharmacology and literature research revealed that QTSC contained 78 active components that acted on 73 target genes,reg-ulating eight signaling pathways,including PI3K-Akt,mTOR,MAPK,and IL-17,to exert therapeutic effects on FC.These pathways were mainly involved in biological processes such as cell apoptosis and gene expression regulation.Molecular docking results showed that active components such as quercetin,luteolin,and emodin had high binding affinity with PIK3CG and AKT1.In animal experiments,compared to the normal control group,the model control group showed significantly reduced fecal weight,water content,and small intestinal propulsion rate(P<0.05 or P<0.01),and significantly downregulated protein expression levels of p-PI3K,p-Akt,PI3K,and Akt in colon tissue(P<0.01).Compared to the model control group,the QTSC groups showed significant increases in fecal weight,water content,and small intestinal propul-sion rate(P<0.05 or P<0.01).In the QTSC 1.0 g/kg group,plasma levels of GAS and MTL were significantly elevated(P<0.01),and protein expression levels of p-PI3K,p-Akt,PI3

关 键 词：芪黄通秘软胶囊 功能性便秘 网络药理学 分子对接 动物实验 磷脂酰肌醇3-激酶/蛋白激酶B信号通路 

分 类 号：R285.5[医药卫生—中药学]