肝纤维化能够保护小鼠抵抗D-GalN/LPS诱导的致死性损伤  

Liver fibrosis protects mice against lethal injury induced by D-GalN/LPS

作　　者：白丽[1] 孔明[1] 张晓慧[1] 丁美[1] 郑素军[1] 陈煜[1] 段钟平[1] 

机构地区：[1]首都医科大学附属北京佑安医院人工肝中心,北京市100069

出　　处：《世界华人消化杂志》2014年第14期1998-2002,共5页World Chinese Journal of Digestology

基　　金：国家"十二五"科技重大专项基金资助项目;Nos.2012ZX10002004-006;2012ZX10004904-003-001;2013ZX10002002-006-001;北京市卫生系统高层次卫生技术人才基金资助项目;No.2011-3-083;首都医科大学基础-临床合作基金资助项目;Nos.14JL72;14JL73~~

摘　　要：目的:证明四氯化碳(carbon tetrachloride,CCl4)诱导的肝纤维化小鼠对致死性D-氨基半乳糖/脂多糖(D-galactosamine and lipopolysaccharide,D-GalN/LPS)攻击的耐受性.方法:建立CCl4诱导的肝纤维化小鼠模型,于纤维化6 wk时以致死剂量的D-GalN(700 mg/kg)/LPS(50μg/kg)进行攻击,以同样处理的正常小鼠作为对照,即实验共分为4组:正常对照组(Nor)、急性损伤组(Nor+D-GalN/LPS)、肝纤维化组(Fib)、肝纤维化+急性攻击组(Fib+D-GalN/LPS).根据攻击前后小鼠生存率、转氨酶水平及肝组织学的变化来评估正常和纤维化小鼠对致死性D-GalN/LPS损伤的耐受性.结果:生存分析显示,Fib+D-GalN/LPS组的生存率显著高于Nor+D-GalN/LPS组(100%vs20%).血清转氨酶结果表明,Fib+D-GalN/LPS组肝损伤程度明显轻于Nor+D-GalN/LPS组,其sALT水平分别为(6630 U/L±1675 U/L)和(22429 U/L±5446 U/L)(P<0.01).接受攻击的纤维化和正常小鼠的sALT分别升高了14.3倍和455.9倍.肝组织学检查结果也证明,接受致死性D-GalN/LPS攻击的纤维化小鼠的肝损伤较同样处理的正常小鼠明显减轻.结论:CCl4诱导的肝纤维化可保护小鼠抵抗致死性D-GalN/LPS损伤的攻击.AIM： To assess the tolerance of mice with carbon tetrachloride（CCl4）-induced fibrosis to a lethal dose of D-galactosamine/lipopolysaccharide（DGalN/LPS）. METHODS： A mouse model of hepatic fibrosis was established by intraperitoneal injection ofCCl4（in mineral oil）, twice a week for 6 wk. At the end of fibrosis induction, mice were challenged intraperitoneally with D-GalN（700 mg/kg）/LPS（50 μg/kg）. Normal mice treated in the same way were used as controls. Mice were sacrificed 24 h after acute insult. Sera and liver tissues were harvested for analyses. To evaluate the tolerance of normal and fibrotic mice to a lethal dose of D-GalN/LPS, survival rate, serum alanine aminotransferase（sALT） levels and histological changes of the liver were compared between before and after acute challenge.RESULTS： The survival rate of fibrotic mice subjected to a lethal dose of D-GalN/LPS was significantly higher than that of normal mice treated in the same way（100% vs 20%）. After challenged by D-GalN/LPS, sALT in normal mice increased by 455.9 folds（49.2 U/L ± 12.9 U/L vs 22429 U/L ± 5446 U/L, P 0.01）, which was significantly higher than that in fibrotic mice（14.3 folds） [（463.7 U/L ± 109.0 U/L vs 6630 U/L ± 1675 U/L, P 〈0.01）. The tolerance of fibrotic mice to D-GalN/LPS was confirmed by well-preserved liver architecture as compared with controls. CONCLUSION： CCl4-induced liver fibrosis protects mice against a lethal dose of D-GalN/LPS.

关 键 词：肝纤维化 损伤 耐受 

分 类 号：R575.2[医药卫生—消化系统]