IL-33及其受体ST2在D-GalN/LPS诱导的急性肝功能衰竭小鼠中的表达及意义  

The expression profiles and significance of IL-33 and its receptor ST2 in a murine model of D-GalN/LPS-induced acute liver failure

作　　者：姜绍文[1] 林兰意[1] 项晓刚[1] 卢捷[1] 王芃[1] 莫瑞东[1] 刘昱含[1] 蔡伟[1] 王晖[1] 谢青[1] 

机构地区：[1]上海交通大学医学院附属瑞金医院感染科,200025

出　　处：《肝脏》2016年第4期267-272,共6页Chinese Hepatology

基　　金：国家自然科学基金(81171569;81300316;81570535);国家十二五重大专项(2012ZX10002003-003;2012ZX10002007-002.2012ZX10002007-003-008);国家临床重点专科建设项目(感染病学);上海市卫生和计划生育委员会课题(20144329);上海市学科带头人计划(12XD1403600);中国肝炎防治基金会王宝恩肝纤维化研究基金项目(CFHPC20131056)

摘　　要：目的研究D-GalN/LPS诱导的急性肝衰竭小鼠中IL-33及其受体ST2的表达及意义。方法腹腔注射DGaIN(900 mg/kg)/LPS(10μg/kg)诱导急性肝衰竭小鼠模型。通过q-PCR、Westcrn印迹、ELISA、免疫组织化学染色等实验技术检测IL-33及其受体ST2在不同时间点的动态变化。结果急性肝衰竭小鼠肝内的IL-33 mRNA水平随着肝损伤加重不断增高,肝衰竭时上升至峰值,D-GalN/LPS诱导后7 h,肝组织表现为明显坏死。而肝内ST2L受体蛋白含量在DGalN/LPS诱导后3 h,未出现明显的肝细胞损伤前已显著升高,之后不断下降,到7 h肝衰竭时其水平降至最低。此外,外周血清中IL-33蛋白水平亦随时间持续升高,在7 h肝衰竭时达高峰,与IL-33 mRNA的动态变化相一致。然而血清sST2蛋白水平在0 h和3 h肝细胞损伤的早期无明显差异,但在5 h肝细胞损伤的中期却显著升高,之后又显著降低。免疫组织化学染色显示急性肝衰竭小鼠肝内IL-33来源于血管内皮细胞和肝血窦细胞核内。结论 IL-33及其受体ST2随时间的动态变化与急性肝衰竭的病情进展存在紧密联系,提示IL-33/ST2轴参与了急性肝衰竭的发生发展过程。Objective To investigate the expression profiles and implication of IL-33 and its receptor ST2 in a murine model of acute liver failure（ALF） induced by D-GalN/LPS.Methods The ALF murine model was set up by intraperitoneal injection of D-GalN（900 mg/kg）/LPS（10 ug/kg）.and confirmed by histopathology and biochemistry.Dynamic expression profiles of IL-33 and its receptor ST2 in ALF murine model were investigated by quantitative polymerase chain reaction（qPCR）.western-blot,enzyme-linked immune-sorbent assay（ELISA） and immunohistochemistry at different time points,respectively.Results The murine model of ALF was successfully established by intraperitoneal injection of D-GalN（900mg/kg）/LPS（10 ug/kg）.The mRNA level of inlra-hepatic IL-33 continuously increased with the progression of ALF,and reached the peak at 7 h after D-GalN/LPS challenge.Compared to baseline,intra-hepatic ST2 L protein level was markedly up-regulated at 3 h.which was before the occurrence of obvious hepatocytes damage.However,it declined later on and fall to the lowest at 7 h.In addition,it was observed that IL-33 protein level in serum was elevated sustainedly over lime and reached the highest level at 7 h.which was consistent with its dynamic mRNA changes.In contrast,the serum level of sST2 had no significant differences between 0 h and 3 h at the early stage of liver damage,but showed an obvious rise to climax at 5 h in the medium-term of liver damage,and then was followed by a drastic decline.The immunohistochemistry results confirmed that intra-hepatic IL-33 was mainly located in the nucleus of endothelial cells and sinusoidal cells in ALF mouse liver.Conclusion The dynamic changes of IL-33 and its receptor ST2 in ALF mice arc closely linked with the progression of acute liver failure,suggesting that IL-33/ST2 axis is indeed involved in the process of ALF.This might provide a novel potential target for ALF treatment.

关 键 词：IL-33 ST2L sST2 急性肝功能衰竭 动态表达 

分 类 号：R575.3[医药卫生—消化系统]