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

作　　者：林海佳[1] 苏志恒[1] 何颖 黎银凤 韦锦斌[1] Lin Haijia;Su Zhiheng;He Ying;Li Yinfeng;Wei Jinbin(Pharmaceutical College,Guangxi Medical University,Nanning 530021,China)

机构地区：[1]广西医科大学药学院,南宁530021

出　　处：《广西医科大学学报》2023年第5期733-741,共9页Journal of Guangxi Medical University

基　　金：国家自然科学基金资助项目(No.81960767);广西老年病防治药物基础研究重点实验室资助项目(No.20201703);广西生物活性分子研究与评价重点实验室资助项目(No.20214602)。

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。Objective:To observe the effect and mechanism of Abrus cantoniensis Hance on acute liver injury induced 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 resonance-spectroscopy(^(1)H-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-induced 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,leucine,taurine,glucose,glycine,alanine,creatine,etc.,were found by ^(1)H-NMR metabolomic analysis.They were mainly enriched in phenylalanine,tyrosine and tryptophan biosynthesis,taurine and taurine metabolism,glutathione metabolism,glycine,serine and threonine metabolism and other metabolic pathways.Conclusion:Abrus cantoniensis Hance has a protective effect on APAP-induced drug-i

关 键 词：鸡骨草 代谢组学 肝损伤 保护作用 

分 类 号：R285.5[医药卫生—中药学]