【摘要】 目的研究N-乙酰半胱氨酸(NAC)对D-氨基半乳糖(D-GalN)与细菌脂多糖(LPS)引起小鼠急性肝损伤的保护作用。方法建立GalN/LPS引起的小鼠急性肝损伤模型。在GalN与LPS共处理前30min经腹腔注射给予NAC,于GalN/LPS处理1·5h后剖杀部分动物取血,测定血清肿瘤坏死因子α(TNF-α)含量;GalN/LPS处理8h后剖杀剩余动物,取血和肝脏,测定血清丙氨酸氨基转移酶(ALT)活力和一氧化氮(NO)水平,检测肝脏组织Caspase-3活性与还原性谷胱甘肽(GSH)含量,采用DNA断裂分析方法检测肝脏凋亡,并对部分肝脏进行病理组织学检查。结果与GalN/LPS处理组比较,NAC预处理组小鼠血清ALT活力、肝脏Caspase-3活性和GSH损耗均显著下降,肝脏组织病理学改变明显改善,DNA断裂分析未见明显凋亡梯度,而NAC对小鼠血清TNF-α含量和NO生成无显著影响。结论NAC预处理对GalN/LPS引起的小鼠急性肝损伤有保护作用,主要通过其抗凋亡和抗氧化作用。更多还原

【Abstract】 Objective To study the protective effects of N-acetylcysteine(NAC) on GalN/LPS-induced acute liver injury in mice.Methods A model of acute liver injury was induced by injection of D-galactosamine(GalN) in mice given together with a low dose of lipopolysaccharide(LPS).Female CD-1 mice were pretreated with NAC(150 mg/kg,i.p) at 30 min before GalN/LPS co-injection.Mice were sacrificed at 1.5 h and 8 h after GalN/LPS administration.Blood serum was collected for measurements of TNF-α,alanine aminotransferase(ALT),and nitrate plus nitrite,respectively.Livers were dissected for measurements of Caspase-3 activity,GSH content,pathological change,and DNA laddering.Results Pretreatment with NAC significantly alleviated GalN/LPS-induced increased in serum ALT activity,attenuated hepatic GSH depletion,Caspase-3 activity,and DNA degradation,and improved liver pathological changes in mice.However,NAC had no effect on GalN/LPS-induced serum NO production and TNF-α concentration.Conclusion NAC pretreatment attenuates GalN/LPS-induced acute liver injury via its strong antioxidation and anti-apoptotical effects.更多还原