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    鸡骨草提取物对对乙酰氨基酚诱导小鼠急性肝损伤保护作用的研究

    Protective effect of Abrus cantoniensis Hance on acetaminophen-induced acute liver injury in mice

      摘要
    • 摘要: 目的：研究鸡骨草提取物对对乙酰氨基酚（APAP）诱导小鼠急性肝损伤的保护作用及其机制。方法：将40 只健康的雄性昆明种小鼠随机分为正常组、模型组、阳性组（200 mg/kg N-乙酰-L-半胱氨酸）、鸡骨草提取物高、低剂量组（60 g/kg、30 g/kg）；连续给药8 d。末次给药5 h 后，除正常组外，其余各组小鼠腹腔注射265 mg/kg APAP 建立肝损伤模型，测定血清及肝脏组织相关生化指标，并对肝脏组织进行病理形态学检查；运用核磁共振氢谱（1H-NMR）代谢组学技术建立肝代谢物谱，分析鸡骨草提取物对APAP 诱导小鼠急性肝损伤肝代谢轮廓变化和潜在生物标志物的影响。结果：与模型组比较，鸡骨草提取物各剂量组均能著降低谷草转氨酶（ALT）、谷丙转氨酶（AST）、丙二醛（MDA）、白介素-6（IL-6）、一氧化氮（NO）、诱导型一氧化氮合酶（iNOS）表达水平（P< 0.05 或P< 0.01），显著升高肝组织超氧化物歧化酶（SOD）、还原型谷胱甘肽（GSH）水平（P< 0.05 或P< 0.01）；鸡骨草提取物高剂量组显著降低肿瘤坏死因子-α（TNF-α）、白介素-1β（IL-1β）水平（P< 0.05 或P< 0.01）；并能改善肝损伤；代谢组学结果显示，共筛选出差异代谢物11 种，分别是谷胱甘肽、亮氨酸、牛磺酸、葡萄糖、甘氨酸、丙氨酸、肌酸等。主要被富集到苯丙氨酸、酪氨酸和色氨酸生物合成，牛磺酸和亚牛磺酸代谢，谷胱甘肽代谢，甘氨酸、丝氨酸和苏氨酸代谢等代谢通路。结论：鸡骨草提取物对APAP诱导小鼠药物性肝损伤具有保护作用，其机制与抗氧化应激及氨基酸代谢、谷胱甘肽代谢和糖代谢等有关。

       

      Abstract: Objective:To observe the effect and mechanism of Abrus cantoniensis Hance on acute liver injury in-duced by acetaminophen (APAP) in mice.Methods:Forty healthy male Kunming mice were randomly divided into normal group, model group, positive group (200 mg/kg N-acetyl-L-cysteine), high and low dose of Abrus cantoniensis Hance groups (60 g/kg, 30 g/kg).After continuous administration for 8 days and five hours after the last administration, except for the normal group, the mice in the other groups were intraperitoneally injected with 265 mg/kg APAP to establish a liver injury model.The serum and liver tissue related biochemical indexes were measured, and the pathological changes of the liver tissue were examined.Hydrogen nuclear magnetic reso-nance-spectroscopy (1H-NMR) metabolomics technique was adopted to establish the liver metabolite profile, and the effect of Abrus cantoniensis Hance on the changes of metabolic profile and potential biomarkers of APAP-in-duced acute liver injury in mice was analyzed.Results:Compared with the model group, Abrus cantoniensis Hance in different doses groups could significantly decrease the levels of alanine aminotransferase(ALT), alanine aminotransferase (AST), malondialdehyde (MDA), interleukin-6 (IL-6), nitric oxide (NO), and inducible nitric oxide synthase (iNOS) (P< 0.05 or P< 0.01), and increase the levels of superoxide dismutase(SOD) and glutathione (GSH) (P< 0.05 or P< 0.01).The high-dose group of Abrus cantoniensis Hance significantly reduced the levels of tumor necrosis factor-alpha (TNF-α) and interleukin-1β(IL-1β) (P< 0.05 or P< 0.01), and could improve the liver injury.The total of eleven varying metabolites, including glutathione, leu-cine, taurine, glucose, glycine, alanine, creatine, etc., were found by1H-NMR metabolomic analysis.They were mainly enriched in phenylalanine, tyrosine and tryptophan biosynthesis, taurine and taurine metabolism, glutathi-one metabolism, glycine, serine and threonine metabolism and other metabolic pathways.Conclusion: Abrus cantoniensis Hance has a protective effect on APAP-induced drug-induced liver injury in mice, and its mecha-nism is related to anti-oxidative stress, amino acid metabolism, glutathione metabolism and glucose metabolism.

       

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