二甲双胍对内毒素性肝损伤的保护效应与过氧化氢酶的关联性研究

Potential Association between the Protective Effects of Metformin and Catalase in Mice with Endotoxic Liver Injury

目的本实验在前期发现二甲双胍可减轻脂多糖/右旋半乳糖胺诱导的内毒素性肝损伤的基础上,进一步探讨二甲双胍保肝效应与过氧化氢酶的可能关联。方法雄性Balb/c小鼠经腹腔注射脂多糖/右旋半乳糖胺诱导急性肝损伤,随后检测二甲双胍对肝内过氧化氢酶活性的影响并观察过氧化氢酶抑制剂氨基三唑可否阻断二甲双胍对肝损伤的保护效应。结果二甲双胍处理可提高脂多糖/右旋半乳糖胺暴露小鼠肝内过氧化氢酶活性、降低过氧化氢及丙二醛水平。过氧化氢酶抑制剂氨基三唑可明显消除二甲双胍对模型小鼠肝内过氧化氢酶活性的增强作用,但氨基三唑仅能部分消除二甲双胍对过氧化氢水平的抑制作用,氨基三唑不能消除二甲双胍对丙二醛生成、血浆丙氨酸氨基转移酶和天冬氨酸氨基转移酶升高的抑制效应,氨基三唑也不能消除二甲双胍对模型小鼠肝组织病变的改善效应。结论本实验结果提示二甲双胍可增强脂多糖/右旋半乳糖胺暴露小鼠肝组织内过氧化氢酶活性,但这一效应在二甲双胍的保肝效应中不具有重要意义。

OBJECTIVE We previously found the hepatoprotective effects of metformin （Met） in mice with lipopolysaccharide/D- galactosamine （LPS/D-Gal）-induced endotoxic liver injury, the present studies were designed to further explore the potential associa- tion between the hepatoprotective effects of Met and catalse （CAT）. METHODS Acute liver injury was induced by intraperitoneal injection of LPS/D-Gal. The activity of hepatic CAT was determined and whether the CAT inhibitor aminotriazole （ATZ） could abolish the protective effects of Met was tested. RESULTS Met enhanced the activity of CAT in the liver of LPS/D-Gal-exposed mice, sup- pressed the elevation of hydrogen peroxide （ H202 ） and malondialdehyde （MDA）. The CAT inhibitor ATZ obviously suppressed the stimulatory effects of Met on CAT activity, but ATZ partially reversed the suppressive effects of Met on H202 content. ATZ did not re- verse the inhibitory effects of Met on MDA production or ALT and AST elevation, it has no effects on morphological abnormalites. CONCLUSION These data suggest although Met can improve the activity of CAT in LPS/D-Gal challenged mice, these effects seem not important for the protective benefits of Met.