| 摘要: |
| 目的：基于网络药理学与实验研究探讨枳葛保肝降脂方治疗酒精性肝病(ALD)的可能作用机制。方法：筛选枳葛保肝降脂方的潜在有效成分，通过蛋白质-蛋白质相互作用（PPI）网络、基因本体（GO）功能、京都基因与基因组百科全书（KEGG）通路富集分析、分子对接及实验研究对核心靶点、通路等进行验证。通过HE病理染色、ELISA、PCR、Western Blot等方法检测枳葛保肝降脂方对ALD大鼠肝组织及血清相关指标的影响。结果：获得枳葛保肝降脂方靶点321个，ALD相关基因1 635个，交集基因178个，其中核心靶点15个。核心靶点基因包括人细胞质肌动蛋白1（ACTB）、白细胞介素- 6（IL-6）等。GO功能主要涉及调控外来生物刺激、氧化应激、肽反应等多种生物过程。KEGG通路主要富集在磷脂酰肌醇3-激酶/蛋白激酶B（PI3K/Akt）信号通路、肿瘤坏死因子（TNF)信号通路、白细胞介素17（IL-17）信号通路等。葛根素、木犀草素可能是枳葛保肝降脂方治疗ALD的核心活性化合物。HE染色结果显示，模型组大鼠部分肝细胞排列紊乱，肝细胞坏死，并伴有大量的脂滴空泡；与模型组相比，各治疗组大鼠肝组织病变均有不同程度的改善。模型组白细胞介素6(IL-6)、肿瘤坏死因子 α(TNF-α)、TNF-α mRNA、IL-6 mRNA及蛋白磷脂酰肌醇3-激酶(PI3K)、磷酸化磷脂酰肌醇3-激酶 (p-PI3K)、蛋白激酶 B(AKT)、磷酸化蛋白激酶 B(p-AKT)水平与正常组比较，美他多辛组及中药各剂量组IL-6、TNF-α、IL-6 mRNA、TNF-α mRNA及蛋白PI3K、p-PI3K、AKT、p-AKT水平与模型组比较，差异均有统计学意义（P＜0.01或P＜0.05）。结论：枳葛保肝降脂方通过多成分、多靶点、多信号通路治疗ALD，可以通过上调p-PI3K、p-AKT的表达，抑制炎症进而起到治疗 ALD的作用。 |
| 关键词: 酒精性肝病 枳葛保肝降脂方 网络药理学 分子对接 体外实验 作用机制 |
| DOI： |
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| Mechanism of action of Zhige Baogan Jiangzhi prescription in treatment of alcoholic liver disease：A study based on network pharmacology and in vitro experiments |
| HUANG Xu,LONG Yu,LI Bo |
| (The Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University，Luzhou 646000，Sichuan，China) |
| Abstract: |
| Objective：To investigate the possible mechanism of action of Zhige Baogan Jiangzhi prescription in the treatment of alcoholic liver disease (ALD) based on network pharmacology and in vitro experiments.Methods：The potential effective constituents of Zhige Baogan Jiangzhi prescription were obtained，and the core targets and pathways were validated based on the protein-protein interaction network，gene ontology (GO) functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis，molecular docking，and experimental study.The methods such as HE pathological staining，ELISA，PCR，and Western blot were used to investigate the effect of Zhige Baogan Jiangzhi prescription on related indicators in liver tissue and serum of ALD rats.Results：A total of 321 targets of Zhige Baogan Jiangzhi prescription and 1 635 ALD-related genes were obtained，with 178 intersecting genes and 15 core targets.The core targets included ACTB and IL-6.GO functions mainly involved various biological processes such as regulation of external biological stimulus，oxidative stress，and peptide response，and KEGG pathways were mainly enriched in the PI3K/Akt signaling pathway，the TNF signaling pathway，and the IL-17signaling pathway.Puerarin and luteolin might be the core active compounds of Zhige Baogan Jiangzhi prescription in the treatment of ALD.HE staining showed that the model group had disordered arrangement and necrosis of hepatocytes，with a large amount of lipid droplet vacuoles，and compared with the model group，each treatment group had varying degrees of improvement in liver lesions.There were significant differences in the protein and mRNA expression levels of IL-6 and TNF-α and the protein expression levels of PI3K，p-PI3K，AKT，and p-AKT between the model group and the normal group，as well as between the metadoxine group and each traditional Chinese medicine group (P＜0.01 or P＜0.05）.Conclusion：Zhige Baogan Jiangzhi prescription exerts a therapeutic effect on ALD through multiple components，targets，and signaling pathways，possibly by upregulating the expression levels of p-PI3K and p-AKT and inhibiting inflammation. |
| Key words: alcoholic liver disease Zhige Baogan Jiangzhi prescription network pharmacology molecular docking in vitro experiment mechanism of action |
