褪黑素、莫达非尼对小鼠试验性急性肝衰竭的影响  

Effect of melatonin and modafinil on acute hepatic failure in mice

作　　者：朱海鹏[1] 谭德明[2] 侯周华[2] 

机构地区：[1]华南大学湘雅医院内科,湖南长沙410008 [2]华南大学湘雅医院感染病科,湖南长沙410008

出　　处：《中国现代医学杂志》2005年第19期2943-2947,共5页China Journal of Modern Medicine

摘　　要：目的研究褪黑素、莫达非尼对小鼠试验性急性肝衰竭的影响。方法雄性昆明小鼠,给予D-半乳糖胺(D-GalN)和脂多糖(LPS)同时腹腔注射,制备小鼠急性肝衰竭模型;并于造模前2h,治疗组分别给予相应药物灌胃,对照组给予蒸馏水灌胃。比较各组小鼠的24h存活率,血清转氨酶水平,肝脏组织病理学改变,血清中TNF-α、IL-1的水平,肝脏组织中SOD、MDA、GR、GSH、NO、NOS的水平。结果D-GalN/LPS可以导致小鼠急性肝衰竭;褪黑素可以提高小鼠存活率,减轻肝脏病变程度,降低血清转氨酶活性及TNF-α、IL-1的浓度,增加肝脏组织中SOD、GR的活性,降低NOS的活性及MDA、NO的浓度。莫达非尼可加重肝脏病变程度,升高血清转氨酶的活性及TNF-α、IL-1的浓度,降低肝脏组织中SOD、GR的活性及升高MDA的浓度。结论褪黑素可减轻D-GalN/LPS所致的急性肝衰竭,提高小鼠的存活率,莫达非尼可加重小鼠的肝损伤。其作用机制可能与两药影响睡眠从而影响炎性细胞因子(如TNF-α、IL-1)的释放和机体氧化能力的改变有关。[Objective] To investigate the effect of melatonin and modafinil on acute hepatic failure in mice. [Methods] Acute liver failure was induced in male Kunming strain mice by enterocoelia injection of D-Gal N and LPS .The melatonin and modatinil were given orally to the mice in treatment groups 2 hr before administration of D- Gal N and LPS, and the same dose of distilled water were given orally to the mice in control group. The 24-hr survival rate, serum alanine aminotransferase（ALT）, aspartate aminotransferase（AST） levels were compared. Serum levels of TNF-α and IL-1 and the levels of SOD, MDA, GR, GSH, NO and NOS in the liver were determined. [Results] D-Gal N and LPS could cause a acute hepatic failure. Treatment with melatonin increased survival rate and im- proved liver histological feather in acute hepatic failure mice induced by D-Gal N and LPS. melatonin inhibited serum levels of ALT, AST, TNF-α and IL-1, and reduced levels of MDA, NO and NOS and increased levels of GR and SOD in the liver. Modafinil worsened liver damage, elevated serum levels of ALT, AST, TNF-α and IL-1, increased level of MDA and inhabited SOD, GR activity in the liver. [ Conclusion ] Treatment with melatonin could improved the D-Gal N/LPS-indueed acute hepatic failure but modafinil deteriorated it. It was suggested that melatonin could improved progress of acute hepatic failure by affecting production of inflammatory eytokines （such as TNF-α and IL-1） and alterring oxidation in acute hepatic failure mice induced by D-Gal N and LPS.

关 键 词：褪黑素 莫达非尼 急性肝衰竭 睡眠 

分 类 号：R575.3[医药卫生—消化系统]