N-乙酰半胱氨酸对GalN/LPS引起小鼠急性肝损伤的保护作用  

N-acetylcysteine protects against GalN/LPS-induced acute liver injury in mice

作　　者：王华[1] 徐德祥[1] 吕金伟[1] 宁萑[1] 赵磊[1] 陈远华[1] 张程[1] 李祥云[1] 

机构地区：[1]安徽医科大学卫生毒理学系,合肥230032

出　　处：《安徽医科大学学报》2007年第3期275-278,共4页Acta Universitatis Medicinalis Anhui

基　　金：安徽医科大学校基金(编号:2006kj13);国家自然科学基金(编号:30371667;30572223;30671786)

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。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 （GAIN） 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.

关 键 词：乙酰半胱氨酸/药理学 多糖类 细菌/药理学 肝/损伤 抗氧化剂 

分 类 号：R575[医药卫生—消化系统] R977.7[医药卫生—内科学]