网络药理学视角下果胶及其代谢产物调控山羊子宫内膜异位症的作用靶点及通路解析

doi:10.16431/j.cnki.1671-7236.2025.12.042

摘要/Abstract

摘要： 【目的】本研究基于网络药理学和分子对接技术，探讨了果胶及其代谢产物短链脂肪酸调控山羊子宫内膜异位症的作用靶点及通路调控机制。【方法】通过中药系统药理学数据库(TCMSP)、PharmMapper、SwissTargetPrediction和SEA数据库预测果胶及其代谢产物短链脂肪酸的潜在作用靶点，并结合GeneCard、DisGeNET、TTD、DrugBank及OMIM等数据库获取山羊子宫内膜异位症相关潜在靶点。利用Venny 2.1工具筛选出果胶及其代谢产物短链脂肪酸与山羊子宫内膜异位症的交集靶点，构建蛋白互作(PPI)网络并识别核心靶点；通过DAVID数据库进行GO功能和KEGG通路富集分析。进一步利用Autodock Tools 1.5.7软件对果胶及其代谢产物短链脂肪酸与核心作用靶点进行分子对接模拟，验证其结合能力。【结果】共筛选出501个果胶靶点、490个短链脂肪酸靶点及3 641个疾病靶点，其交集靶点为26个。PPI网络分析结果显示，雄激素受体(AR)、细胞周期蛋白依赖性激酶1(CDK1)、信号传导及转录激活蛋白 3(STAT3)、表皮生长因子受体(EGFR)、热休克蛋白90AA1(HSP90AA1)、过氧化物酶体增殖物激活受体γ(PPARγ)、成纤维细胞生长因子2(FGF2)和过氧化物酶体增殖物激活受体α(PPARα)为药物作用于疾病的核心靶点。GO功能富集分析显示，生物过程富集10个条目，细胞组分富集1个条目，分子功能富集3个条目。KEGG通路富集分析表明，果胶及其代谢产物主要通过调控EGFR酪氨酸激酶抑制剂、PI3K-Akt信号通路、PPAR信号通路和孕酮介导的卵母细胞成熟等关键通路，从而调控山羊子宫内膜异位症。分子对接结果显示，果胶及其代谢产物短链脂肪酸与核心靶点(AR和PPARγ)的结合能均＜－20 kJ/mol。【结论】本研究预测结果显示，果胶及其代谢产物短链脂肪酸通过作用于AR、CDK1、STAT3、EGFR、HSP90AA1、PPARγ、FGF2和PPARα等核心靶点，调控EGFR酪氨酸激酶抑制剂、PI3K-Akt等关键信号通路，抑制细胞增殖、促进凋亡，从而缓解山羊子宫内膜异位症。本研究结果为果胶作为膳食纤维在山羊繁殖中的应用提供了重要的理论依据。

关键词: 果胶; 短链脂肪酸; 山羊; 子宫内膜异位症; 网络药理学; 分子对接

Abstract: 【Objective】 Based on network pharmacology and molecular docking techniques,this study explored the therapeutic targets and pathway regulatory mechanisms of pectin and its metabolite short-chain fatty acids (SCFAs) in regulating goat endometriosis. 【Method】 Potential targets of pectin and SCFAs were predicted using the traditional Chinese medicine systems pharmacology database (TCMSP),PharmMapper,SwissTargetPrediction,and SEA databases.Disease-related targets for goat endometriosis were obtained from the GeneCard,DisGeNET,TTD,DrugBank and OMIM databases.The intersection targets of pectin,SCFAs and goat endometriosis were screened using the Venny 2.1 tool,and a protein-protein interaction (PPI) network was constructed to identify core targets.GO functional and KEGG pathway enrichment analysis was performed using DAVID database.Molecular docking simulations between pectin,SCFAs and core targets were conducted using Autodock Tools 1.5.7,to validate their binding affinity. 【Result】 A total of 501 pectin targets,490 SCFA targets,and 3 641 disease targets were screened,with 26 intersection targets identified.PPI network analysis revealed that androgen receptor (AR),cyclin-dependent kinase 1 (CDK1),signal transducer and activator of transcription 3 (STAT3),epidermal growth factor receptor (EGFR),heat shock protein 90 alpha family class A member 1 (HSP90AA1),peroxisome proliferator-activated receptor gamma (PPARγ),fibroblast growth factor 2 (FGF2),and peroxisome proliferator-activated receptor alpha (PPARα) were the core targets of the drug-disease interaction.GO functional analysis (P＜0.05) showed enrichment in 10 biological processes,1 cellular component,and 3 molecular functions.KEGG pathway enrichment analysis indicated that pectin and its metabolites primarily regulated goat endometriosis by influencing key pathways such as EGFR tyrosine kinase inhibitor resistance,PI3K-Akt signaling pathway,PPAR signaling pathway,and progesterone-mediated oocyte maturation.Molecular docking results demonstrated that the binding energies between pectin,SCFAs and core targets (AR and PPARγ) were all less than －20 kJ/mol. 【Conclusion】 The predicted results of this study showed that,pectin and its metabolite SCFAs alleviated goat endometriosis by targeting AR,CDK1,STAT3,EGFR,HSP90AA1,PPARγ,FGF2,and PPARα,and regulating key signaling pathways such as EGFR tyrosine kinase inhibitor resistance and PI3K-Akt,thereby inhibiting cell proliferation and promoting apoptosis.This study provided a theoretical foundation for the application of pectin as a dietary fiber in goat reproduction.

Key words: pectin; short chain fatty acids; goat; endometriosis; network pharmacology; molecular docking

中图分类号:

S853.74

义拉勒特, 陈鹏, 萨初拉, 张春华, 王博, 金鹿, 李胜利, 杨鼎, 孙余卓, 孙海洲. 网络药理学视角下果胶及其代谢产物调控山羊子宫内膜异位症的作用靶点及通路解析[J]. 中国畜牧兽医, 2025, 52(12): 5993-6006.

Yilalete, CHEN Peng, SA Chula, ZHANG Chunhua, WANG Bo, JIN Lu, LI Shengli, YANG Ding, SUN Yuzhuo, SUN Haizhou. Analysis of the Targets and Pathways of Pectin and Its Metabolites Regulating Endometriosis in Goats from the Perspective of Network Pharmacology[J]. China Animal Husbandry & Veterinary Medicine, 2025, 52(12): 5993-6006.

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