【摘要】 目的研究N-乙酰半胱氨酸(NAC)对小鼠急性酒精性肝损伤的影响。方法实验1,乙醇处理组小鼠经口给予6 g/kg的乙醇。小鼠分别于乙醇处理后3、6、9、12 h处死,取血和肝脏组织。实验2,乙醇处理组小鼠经口给予6 g/kg的乙醇,NAC预处理组小鼠于乙醇处理前30 min经腹腔给予NAC(150 mg/kg,ip),NAC后处理组小鼠于乙醇处理后4 h给予NAC(150 mg/kg,ip),2个对照组均给予等容积生理盐水或NAC。小鼠于乙醇处理后6 h处死,取血和肝脏组织。结果小鼠给予乙醇后,血清ALT活力显著升高,且呈明显时间-效应关系;NAC预处理显著抑制乙醇引起血清ALT活力升高,NAC后处理加重乙醇引起的肝损伤;NAC预处理组肝脏组织MDA水平显著低于单纯乙醇处理组,而NAC后处理组肝脏组织MDA水平显著高于单纯乙醇处理组;NAC预处理组肝脏组织GSH含量显著高于单纯乙醇处理组,NAC后处理组肝脏组织GSH含量与单纯乙醇处理组相比无明显差异。进一步研究发现,小鼠经口给予乙醇显著上调肝脏组织TNF-αmR-NA表达。结论NAC预处理通过抑制乙醇引起的氧化应激和肝TNF-αmRNA表达,预防急性酒精性肝损伤;NAC后处理加重乙醇引起的急性肝损伤。更多还原

【Abstract】 Objective To investigate the effects of N-acetylcysteine(NAC) on acute ethanol-induced liver damage in mice.Methods Experiment one: mice were administered by gavage with a single dose of ethanol(6 g/kg) and sacrificed at 3,6,9,and 12 h after ethanol.Experiment two: All mice except controls(either saline or NAC) were administered by gavage with a single dose of ethanol(6 g/kg).In Ethanol+NAC groups,the mice were treated with NAC(150 mg/kg,i.p.) at 30 min before ethanol or 4 h after ethanol.The mice were sacrificed either at 6 h after ethanol treatment.Results Ethanol administration at a dose of 6 g/kg caused a significant increase in serum ALT activity in a time-dependent manner.Acute ethanol-induced liver damage was associated with increased MDA and TNF-α mRNA levels and decreased GSH contents in mouse liver.Pretreatment with NAC significantly attenuated acute ethanol-induced lipid peroxidation and GSH depletion,inhibited hepatic TNFα mRNA expression,and protected against acute ethanol-induced liver damage.Conclusions Pretreatment with NAC protects against acute ethanol-induced liver damage.But administered after ethanol,NAC behaves as a prooxidant and aggravates acute ethanol-induced liver damage.更多还原