脂肽对Con A诱导的小鼠急性肝损伤的保护作用  

Lipopeptide protects against acute liver injury induced by concanavalin A in C57BL/6 mice

作　　者：姚雪莲[1] 王磊[2] 张文[2] 詹轶群[3] 葛常辉[1,3] 

机构地区：[1]安徽医科大学,合肥230032 [2]天津大学,天津300072 [3]军事医学科学院放射与辐射医学研究所,北京100850

出　　处：《军事医学》2016年第5期366-369,378,共5页Military Medical Sciences

基　　金：国家重大科学研究计划资助项目(2013CB910803)

摘　　要：目的研究脂肽在伴刀豆球蛋白A(Con A)诱导的小鼠急性肝损伤的保护作用并探讨相关作用机制。方法应用尾静脉注射Con A构建小鼠急性肝损伤模型,以腹腔注射脂肽方式给药,观察小鼠的存活率,并检测血液中转氨酶水平,分析肝组织病理切片,统计坏死面积,同时对肝内炎症因子的表达水平进行检测。结果脂肽H6101对Con A引起的小鼠急性肝损伤有明显保护作用。降低Con A引起的小鼠死亡率达40%,12 h检测丙氨酸转氨酶(ALT)和天冬氨酸转氨酶(AST)的水平降低达50%。而实时定量PCR结果显示脂肽给药组中炎症因子IFN-γ、IL-6、TNF-α的表达水平分别降低了83.8%、99.3%和99.1%。肝脏病理学分析结果显示,Con A模型组与脂肽给药组相比,小鼠肝坏死面积由14.4%降到6%,差异显著(P<0.01)。表明脂肽对于Con A引起的肝坏死情况有较明显改善。结论脂肽对Con A引起的小鼠急性肝损伤具有明显的保护作用。Objective To evaluate the protective effects of lipopeptide（ H6101 or CBLB612） in mice acute hepatic injury induced by concanavalin A injection and the underlying mechanisms. Methods The protective effects of lipopeptide on Con A-induced hepatic injury were assessed by the survival rate,serum ALT and AST levels,liver histopathological examination,as well as intrahepatic mRNA expression levels of inflammatory cytokines. Results The results demonstrated that lipopeptide H6101 exerted strong protection efficacy on Con A-induced acute liver injury. The mortality rate was reduced 40%. The serum aminotransferase was much lower in lipopeptide H6101 treated mice. A 50% deduction for ALT and AST was observed. A profound reduction of intrahepatic pro-inflammatory cytokine mRNA including IFN-γ（ 83. 8%）,IL-6（ 99. 3%） and TNF-α（ 99. 1%） was detected after Con A injection by quantitative real-time PCR assay,compared with saline treated animals. Additionally, histological examination displayed that lipopeptide treatment significantly attenuated Con A-induced liver tissue necrosis（ 6. 0% necrotic area versus 14. 4% in saline-treated animals） Conclusion Lipopeptide exhibits significant protection effects against Con A-induced acute hepatic injury.

关 键 词：丙氨酸转氨酶 白细胞介素6 肿瘤坏死因子 H6101 伴刀豆球蛋白A 急性肝损伤 NF-κB 

分 类 号：R575[医药卫生—消化系统]