AMPK激活剂下调爆发性肝炎小鼠肝内组织因子表达  

AMPK activator down-regulates the expression of tissue factor in fulminant hepatitis mice

作　　者：代洁[1] 林玲[2] 周丹[2] 艾青[3] 葛璞 张力[2,4] 

机构地区：[1]重庆文理学院校医院,重庆402160 [2]重庆医科大学病理生理学教研室,重庆400016 [3]重庆医科大学生理学教研室,重庆400016 [4]重庆医科大学干细胞与组织工程研究室,重庆400016

出　　处：《生理学报》2016年第1期35-40,共6页Acta Physiologica Sinica

基　　金：supported by the National Natural Science Foundation of China(No.81370179);the Science and Technology Research Project from Chongqing Municipal Education Commission,China(No.KJ1400235)

摘　　要：腺苷酸活化蛋白激酶(AMP activated protein kinase,AMPK)是重要的代谢调节酶及炎症调控新靶点。以往研究显示,AMPK激活剂5-氨基咪唑-4-甲酰胺核苷酸转甲酰酶(5-amino-4-imidazolecarboxamide riboside,AICAR)可通过抑制炎症反应减轻脂多糖/右旋半乳糖胺(lipopolysaccharide/D-galactosamine,LPS/D-gal)诱导的爆发性肝炎。由于炎症可通过激活凝血反应加重组织损伤,本研究旨在以炎症诱导凝血反应为切入点探讨AICAR保肝效应的机制。腹腔注射LPS/D-gal建立爆发性肝炎小鼠模型,用Western blot检测肝内组织因子(tissue factor,TF)、缺氧诱导因子1-α(hypoxia-inducible factor 1α,HIF-1α)以及细胞核内核因子kappa B(nuclear factor kappa B,NF-κB)p65蛋白表达,用实时定量PCR检测肝细胞促红细胞生成素(erythropoietin,EPO)m RNA表达,用试剂盒检测肝组织乳酸(lactic acid,LA)水平。结果显示,LPS/D-gal可促进小鼠肝细胞内TF蛋白表达,提高细胞核内NF-κB p65水平,上调HIF-1α蛋白及EPO m RNA表达,并提高肝组织LA水平;而AICAR干预后,以上指标均明显下调。以上结果提示,AICAR可通过抑制NF-κB活性下调TF表达及凝血活性,从而减轻肝组织缺氧及代谢紊乱,这可能是AICAR减轻LPS/D-gal诱导的爆发性肝炎的新机制。AMP activated protein kinase（AMPK） is a pivotal metabolic regulatory enzyme and novel target of controlling inflammation. Our previous studies had demonstrated that 5-amino-4-imidazolecarboxamide riboside（AICAR）,an AMPK activator,attenuated lipopolysaccharide（LPS）/D-galactosamine（D-gal）-induced fulminant hepatitis via suppressing inflammatory response. Since inflammation usually activates the coagulation response and aggravates inflammation-induced tissue injury,the present study was to explore the effects of AICAR on inflammation-induced activation of coagulation. Male BALB/c mice received LPS/D-gal intraperitoneal injection were used as fulminant hepatitis model. Western blot was used to detect tissue factor（TF） and hypoxia-inducible factor 1α（HIF-1α） protein expressions in hepatic tissue,as well as nuclear factor kappa B（NF-κB） p65 translocation into the nucleus. Real-time quantitative PCR was used to analyze erythropoietin（EPO） m RNA expression level. Lactic acid（LA） level in hepatic tissue was detected by kit. The results showed that LPS/D-gal induced the enhanced expression of TF,elevation of NF-κB p65 nuclear translocation,up-regulation of HIF-1α and EPO expressions,and increased LA level. These above alterations could be suppressed by AICAR. These results suggest that AICAR may down-regulate LPS/D-gal-induced TF expression（coagulation activity）,and relieve hepatic hypoxia and metabolic disorder via suppressing the activity of NF-κB,which may be a novel mechanism of the beneficial effect of AICAR on LPS/D-gal-induced fulminant hepatitis.

关 键 词：腺苷酸活化蛋白激酶 组织因子 凝血 爆发性肝炎 炎症 

分 类 号：R575.1[医药卫生—消化系统]