基于生物信息学和实验验证探讨首荟通便胶囊治疗便秘的作用机制  

Bioinformatics and Animal Experiments Reveal Mechanism of Shouhui Tongbian Capsules in Treating Constipation

作　　者：梁勇 张齐猛 葛斌 张洋[2] 石宇 路越[2] 张虹玺[2] LIANG Yong;ZHANG Qimeng;GE Bin;ZHANG Yang;SHI Yu;LU Yue;ZHANG Hongxi(Liaoning University of Traditional Chinese Medicine(TCM),Shenyang 110847,China;Tne Third Affiliated Hospital of Liaoning University of TCM,Shenyang 110003,China)

机构地区：[1]辽宁中医药大学,沈阳110847 [2]辽宁中医药大学附属第三医院,沈阳110003

出　　处：《中国实验方剂学杂志》2025年第4期150-157,共8页Chinese Journal of Experimental Traditional Medical Formulae

基　　金：国家自然科学基金面上项目(82174371);辽宁省科学技术计划项目(2022JH2/101300060)。

摘　　要：目的:根据首荟通便胶囊化合物成分研究基础,结合网络药理学和动物实验探究首荟通便胶囊治疗便秘的作用机制。方法:将药物成分导入SwissTargetPrediction预测作用靶点,从疾病数据库收集便秘相关靶点,取交集后构建蛋白质-蛋白质互作(PPI)网络筛选核心靶点,随后进行基因本体(GO)功能和京都基因和基因组百科全书(KEGG)通路富集分析。构建“活性成分-靶点-通路”网络,根据其拓扑参数筛选首荟通便胶囊治疗便秘的核心成分。利用分子对接预测核心成分与关键靶点的结合能力。通过构建便秘小鼠模型验证该药干预便秘的关键通路和靶点。结果:PPI网络得到与便秘有关的前6个关键靶点:蛋白激酶B(Akt1)、B细胞淋巴瘤-2(Bcl-2)、糖原合成酶激酶-3β(GSK-3β)、环加氧酶2(PTGS2)、雌激素受体1(ESR1)、表皮生长因子受体(EGFR)。KEGG通路分析表明,磷脂酰肌醇3-激酶(PI3K)/Akt信号通路富集程度最高。“活性成分-靶点-通路”网络拓扑参数分析筛选出前10个核心成分:酸橙黄酮、异橙黄酮、柚皮素、香叶木素、槲皮素、芹菜素、木犀草素、橘皮素、异丹叶大黄素、大黄酚。分子对接结果显示10个核心成分与6个关键靶点均具有较好的结合能力。动物实验表明,经不同剂量首荟通便胶囊干预后,小鼠首粒排黑便时间、粪便含水量、小肠炭末推进率均显著改善;病理显示给予首荟通便胶囊治疗后,结肠黏膜损伤和腺体排列改善,肌层厚度增加;蛋白免疫印迹法(Western blot)结果表明首荟通便胶囊可显著回调便秘小鼠结肠组织内PI3K/Akt通路介导的凋亡相关分子表达;原位末端标记法(TUNEL)染色显示,首荟通便胶囊干预后结肠的细胞凋亡率明显降低。结论:通过网络药理学和体内实验证实,首荟通便胶囊能够通过多靶点、多通路治疗便秘,可有效干预洛哌丁胺诱导的便秘,改善小鼠便秘指标,降低结肠Objective:To explore the mechanism of Shouhui Tongbian capsules in treating constipation based on the research foundation of its active components combined with network pharmacology and animal experiments.Methods:The drug components were imported into SwissTargetPrediction to predict the targets of Shouhui Tongbian capsules,and constipation-related targets were collected from disease databases.A protein-protein interaction(PPI)network was constructed for the common targets shared by Shouhui Tongbian capsules and constipation to screen key targets,which was followed by gene ontology(GO)function and Kyoto encyclopedia of genes and genomes(KEGG)pathway enrichment analyses.A"bioactive component-target-pathway"network was constructed,and the core components of Shouhui Tongbian capsules in treating constipation were screened based on the topological parameters of this network.Molecular docking was employed to predict the binding affinity of core components to key targets.A mouse model of constipation was constructed to screen the key pathways and targets of the drug intervention in constipation.Results:The PPI network revealed six key constipation-related targets:protein kinase B(Akt1),B-cell lymphoma-2(Bcl-2),glycogen synthase kinase-3β(GSK-3β),cyclooxygenase-2(PTGS2),estrogen receptor 1(ESR1),and epidermal growth factor receptor(EGFR).The KEGG pathway analysis showed that the phosphatidylinositol 3-kinase(PI3K)/Akt signaling pathway was the most enriched.The topological parameter analysis of the"bioactive component-target-pathway"network screened out the top 10 core components:auranetin,isosinensetin,naringin,diosmetin,quercetin,apigenin,luteolin,hesperidin,isorhapontigenin,and chrysophanol.Molecular docking results showed that the 10 core components had strong binding affinity with the 6 key targets.Animal experiments showed that after intervention with different doses of Shouhui Tongbian capsules,the time to the first black stool excretion was reduced and the fecal water content and small intestine charcoal propu

关 键 词：首荟通便胶囊 便秘 网络药理学 分子对接 凋亡 磷脂酰肌醇3-激酶(PI3K)/蛋白激酶B(Akt)信号通路 

分 类 号：R285[医药卫生—中药学] R289[医药卫生—中医学] R256