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目的 基于肝脏代谢组学和网络药理学挖掘鸡骨草保护四氯化碳(CCl4)诱导的小鼠急性肝损伤(ALI)的相关通路及靶点，探究其潜在作用机制。方法 将30只C57BL/6J小鼠随机分成空白组、模型组和鸡骨草组。腹腔注射CCl4构建小鼠ALI模型。利用全自动生化仪检测血清中的谷丙转氨酶(ALT)和谷草转氨酶(AST)水平；通过活力检测试剂盒和酶联免疫吸附法(ELISA)检测肝组织中的超氧化物歧化酶(SOD)活力、丙二醛(MDA)水平、肿瘤坏死因子-α(TNF-α)和白细胞介素-6(IL-6)的表达水平；HE染色观察肝组织病理变化。采用UPLC-Q-TOF-MS/MS非靶向代谢组学检测各组小鼠肝脏组织差异代谢物，并进行富集分析；通过网络药理学预测鸡骨草保护CCl4诱导的小鼠ALI的潜在靶点与通路，并进行代谢物-靶点联合分析。结果 与模型组相比，鸡骨草组血清AST和ALT活性降低(P<0.01)，肝组织SOD活性升高(P<0.05)，MDA含量降低(P<0.05)，炎症因子TNF-α和IL-6水平降低(P<0.01)，肝水肿、炎性细胞浸润有所缓解。肝脏代谢组发现34个差异代谢物为鸡骨草治疗CCl4诱导的小鼠ALI的潜在生物标志物，通路富集分析发现主要涉及嘌呤代谢、谷胱甘肽代谢等6条代谢途径(impact>0.01)。网络药理学共鉴定出ALI与鸡骨草的交集靶点233个，其中关键靶点42个，KEGG富集分析表明其潜在机制可能与PI3K-Akt、ErbB信号通路有关。联合分析显示鸡骨草治疗CCl4诱导的小鼠ALI的核心靶点参与了代谢物的调节。结论 鸡骨草可通过调节内源性代谢产物水平，缓解机体代谢紊乱，抑制炎症因子水平发挥治疗CCl4诱导ALI的作用。
Abstract：Objective To determine the potential mechanism of Abrus cantoniensis Hance (AC) in protecting against carbon tetrachloride (CCl4)-induced acute liver injury (ALI) in mice by mining related pathways and targets based on liver metabolomics and network pharmacology.Methods Thirty C57BL/6J mice were randomly divided into a control group,a model group,and an AC group.A mouse model of ALI was established by intraperitoneal injection of CCl4.The serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were measured with an automatic biochemical analyzer.The activity of superoxide dismutase (SOD),the content of malondialdehyde (MDA),and the expression levels of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in liver tissues were measured with activity detection kits and enzyme-linked immunosorbent assay (ELISA).Pathological changes in the liver tissues were observed by HE staining.Ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS/MS)-based untargeted metabolomics was used to detect differential metabolites in the liver tissues of mice in each group,followed by enrichment analysis.Network pharmacology was used to predict potential targets and pathways of AC in protecting against CCl4-induced ALI,and metabolite-target association was analyzed.Results Compared with the model group,the AC group showed decreased serum AST and ALT activities (P<0.01),increased SOD activity in the liver tissues (P<0.05),decreased MDA content (P<0.05),and reduced levels of inflammatory factors TNF-α and IL-6 (P<0.01).Hepatic edema and inflammatory cell infiltration were alleviated.Liver metabolomics identified 34 differential metabolites as potential biomarkers of AC for CCl4-induced ALI.Pathway enrichment analysis revealed 6 major metabolic pathways (impact>0.01),including purine metabolism and glutathione metabolism.Network pharmacology identified 233 intersection targets between ALI and AC,42 of which were key targets.KEGG enrichment analysis suggested that the potential mechanism might be related to the PI3K-Akt and ErbB signaling pathways.Association analysis showed that the core targets of AC in treating CCl4-induced ALI were involved in the regulation of metabolites.Conclusion AC can exert a therapeutic effect on CCl4-induced ALI by regulating the levels of endogenous metabolites,alleviating metabolic disorders,and inhibiting the production of inflammatory factors.
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基本信息:
中图分类号:R285.5
引用信息:
[1]朱琳,孙惠,赵静玉,等.基于代谢组学和网络药理学探究鸡骨草对四氯化碳诱导急性肝损伤的保护作用及机制[J].中南药学,2026,24(03):39-46.
基金信息:
国家自然科学基金区域创新发展联合基金重点支持项目(No.U23A20521); 国家自然科学基金地区基金项目(No.82360767)
2026-03-19
2026-03-19