【摘要】 目的研究褪黑素(MT)对氨基半乳糖(D-GalN)与细菌脂多糖(LPS)共处理引起小鼠急性肝损伤的保护作用。方法建立GalN/LPS引起的小鼠急性肝脏损伤模型。于GalN/LPS共处理前30min和处理后1h、2h分别经腹腔注射给予MT,经GalN/LPS共处理8h后剖杀动物,取血和肝脏,检测血清丙氨酸氨基转移酶(ALT)活力、肿瘤坏死因子α(TNF-α)和一氧化氮(NO)水平,测定肝脏组织Caspase-3活性、还原性谷胱甘肽(GSH)含量、谷胱甘肽还原酶(GSH-RD)和谷胱甘肽过氧化物酶(GSH-PX)活性,采用DNA梯度分析实验检测肝脏凋亡,并对小鼠部分肝脏进行病理组织学检查。结果与模型组比较,MT处理组小鼠血清ALT活力和TNF-α含量明显下降,肝脏Caspase-3活性、GSH损耗明显降低,肝组织GSH-RD和GSH-PX活性明显升高,DNA凋亡条带较前有所减弱,而MT对体内NO生成无明显影响。结论MT对GalN/LPS引起小鼠急性肝损伤有保护作用,主要通过其抗炎、抗氧化和抗凋亡作用。更多还原

【Abstract】 Aim To investigate the effects of Melatonin(MT) on GalN/LPS-induced acute liver injury in mice.Methods A model of apoptotic liver injury was induced by injection of D-galactosamine(GalN) in mice given together with a low sublethal dose of lipopolysaccharide(LPS).Female CD-1 mice were treated with MT(5.0 mg·kg-1,ip) at 30 min before and MT(2.5 mg·kg-1,ip) at 1 h,2 h after GalN/LPS.Mice were sacrificed at 8 h after GalN/LPS.Blood serum was collected for measurement of alanine aminotransferase(ALT),TNF-α,and nitrate plus nitrite.Livers were dissected for measurements of Caspase-3 activity,GSH content,GSH-PX activity,GSH-RD activity,histological change,and DNA laddering.Results Treatments with MT significantly attenuated GalN/LPS-induced increase in serum ALT activity and TNF-α concentration,alleviated hepatic caspase-3 activity,GSH depletion,and DNA laddering,increased GSH-PX and GSH-RD activity,and improved liver histological change in mice.However,MT had no effect on GalN/LPS-induced serum nitric oxide(NO) production.Conclusions MT attenuates GalN/LPS-induced acute liver injury via its anti-inflammatory,antioxidant,and anti-apoptotic effects.更多还原