【摘要】 目的研究低剂量内毒素(LPS)预处理对LPS介导的小鼠急性肝损伤的影响。方法LPS通过腹腔注射小鼠;丁基亚磺酰亚胺(BSO)处理耗尽小鼠肝脏谷胱苷肽(GSH)含量;血浆天冬氨酸氨基转移酶(AST)和丙氨酸氨基转移酶(ALT)测定用全自动生化分析仪;基因表达测定采用RT-PCR。结果①低剂量LPS预处理降低高剂量LPS诱导的小鼠肝功能损伤;②低剂量LPS刺激肝脏GSH含量升高;LPS预处理组GSH水平显著高于高剂量LPS处理组;③BSO预处理后,LPS预处理组与高剂量LPS组的血浆ALT和AST水平没有差别;④LPS处理导致转硫途径关键酶——胱硫醚β合酶活性以及GSH合成途径关键酶——γ-谷氨酰半胱氨酸合成酶表达升高。结论低剂量LPS通过上调肝组织中GSH合成相关基因表达,增加GSH的含量,减轻高剂量LPS诱导的肝脏损伤。更多还原

【Abstract】 Objective To explore the effect of low-dose lipopolysaccharide(LPS) on acute liver injury induced by high-dose lipopolysaccharide in mice.Methods The mouse model of acute liver injury was reproduced by intraperitoneal administration of LPS.GSH in the livers of mice was depleted by administering buthionine sulphoximine(BSO).Aspartate transaminase(AST) and alanine transaminase(ALT) in the plasma were measured by an automated biochemistry analyzer.The mRNA levels of cystathione(-synthase(CBS) and γ-glutamylcysteine synthetase(GCS) were determined by RT-PCR.Results ① Pre-treatment with low-dose LPS attenuated acute liver injury induced by high-dose LPS in mice.② Low-dose LPS treatment elicited hepatic glutathione(GSH) levels in mice.The levels of GSH in the group pre-treated with low-dose LPS were higher than those in the group treated with high-dose LPS.③ Plasma levels of ALT and AST in the group pre-treated with low-dose LPS were similar to those in the group treated with high-dose LPS.④ Low-dose LPS pre-treatment resulted in an increase in CBS activity as well as GSC mRNA levels.Conclusion Low-dose LPS attenuates acute liver injury induced by high-dose LPS in mice by promoting hepatic GSH levels though up-regulating activity or expression of GSH biosynthesis-relative genes.更多还原