基于网络药理学与实验验证的赶黄草–炙黄芪–生大黄调控IL-11通路改善酒精性肝损伤的机制研究
Mechanistic Study on the Modulation of IL-11 Pathway by Penthorum chinense Pursh-Astragalus membranaceus-Raw Rheum palmatum in Ameliorating Alcoholic Liver Injury Based on Network Pharmacology and Experimental Validation
摘要: 目的：本研究基于“肝与大肠相通”理论，采用网络药理学预测与动物实验验证相结合的策略，探讨赶黄草–炙黄芪–生大黄复方(SHY)干预酒精性肝损伤(ALI)的作用机制。方法：网络药理学获取SHY干预ALI的活性成分及主要靶点，构建PPI网络，进行GO和KEGG富集分析筛选可能涉及的生物过程和信号通路。利用Lieber-DeCarli酒精液体饲料[5% (vol/vol)乙醇]复制野生型(WT)小鼠ALI模型，通过检测体循环血清ALT、IL-11及肝脏组织IL-11和p-STAT3蛋白表达，验证SHY对ALI的保护作用及机制。结果：通过TCMSP数据库筛选共获得15种活性成分及219个药物靶点，与ALI疾病靶点交集得到106个关键靶点。PPI网络分析显示TNF、IL6、AKT1等为核心节点，GO/KEGG富集提示其通过IL-17、TNF等信号通路调控氧化应激与炎症反应。动物实验证实SHY显著降低模型小鼠血清ALT、IL-11水平(P < 0.01)，抑制肝组织p-STAT3磷酸化。Western Blot显示SHY干预后IL-11表达下调1.8倍。结论：本研究首次揭示SHY通过调控IL-11R/JAK/STAT轴改善ALI炎症，为“肝病治肠”理论提供分子生物学依据。
Abstract: Objective: Based on the traditional Chinese medicine theory of “liver-intestine correlation,” this study integrated network pharmacology prediction with experimental validation to investigate the mechanism of the Penthorum chinense Pursh-Astragalus membranaceus-Raw Rheum palmatum compound (SHY) in alleviating alcohol-induced liver injury (ALI). Methods: Network pharmacology was employed to identify active components and key targets of SHY against ALI. Protein-protein interaction (PPI) networks were constructed, followed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses to elucidate biological processes and signaling pathways. ALI was induced in wild-type (WT) mice using the Lieber-DeCarli ethanol liquid diet (5% ethanol, vol/vol). Serum alanine aminotransferase (ALT) and interleukin-11 (IL-11) levels, along with hepatic IL-11 and phosphorylated STAT3 (p-STAT3) protein expression, were measured to validate SHY’s hepatoprotective effects. Results: Fifteen bioactive components and 219 potential targets of SHY were identified from the TCMSP database, with 106 overlapping targets linked to ALI. PPI network analysis revealed TNF, IL6, and AKT1 as core targets. GO/KEGG enrichment highlighted SHY’s regulation of oxidative stress and inflammation via IL-17 and TNF signaling pathways. Animal experiments demonstrated that SHY significantly reduced serum ALT and IL-11 levels (P < 0.01) and suppressed hepatic p-STAT3 phosphorylation. Western blot confirmed a 1.8-fold downregulation of IL-11 expression in SHY-treated mice. Conclusion: This study is the first to demonstrate that SHY ameliorates ALI by modulating the IL-11R/JAK/STAT axis, providing molecular evidence for the “treating liver diseases through intestinal regulation” theory.
文章引用：金晓慧, 于会芳, 赵波, 郭沫容, 严展, 徐林, 陈兰馨, 周显华. 基于网络药理学与实验验证的赶黄草–炙黄芪–生大黄调控IL-11通路改善酒精性肝损伤的机制研究[J]. 中医学, 2025, 14(4): 1770-1779. https://doi.org/10.12677/tcm.2025.144263

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