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

肝脏 ›› 2016, Vol. 21 ›› Issue (4): 267-272.

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

姜绍文, 林兰意, 项晓刚, 卢捷, 王芃, 莫瑞东, 刘昱含, 蔡伟, 王晖, 谢青

200025 上海交通大学医学院附属瑞金医院感染科

收稿日期:2015-12-31 发布日期:2020-05-27
通讯作者: 谢青,Email:xieqingrjh@163.com
基金资助:
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)。

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

JIANG Shao-wen, LIN Lan-yi, XIANG Xiao-gang, LU Jie, WANG Fan, MO Rui-dong, LIU Yu-han, CAI Wei, WANG Hui, XIE Qing

Department of Infectious Disease,Ruijin Hospital Affilicated to Medical Colledg of Shanghai Jiaotong University,Shanghai 200025,China

Received:2015-12-31 Published:2020-05-27
Contact: XIE-Qing,Email:xieqingrjh@163.com

摘要/Abstract

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D-GalN(900 mg/kg)/LPS(10 μg/kg)诱导急性肝衰竭小鼠模型。通过q-PCR、Western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D-GalN/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。

关键词: IL-33, ST2L, sST2, 急性肝功能衰竭, 动态表达

Abstract: 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 (q-PCR), 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 (900 mg/kg)/LPS(10 ug/kg). The mRNA level of intra-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 ST2L 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 time 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 are 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.

Key words: IL-33, ST2L, sST2, ALF, Dynamic expression

姜绍文, 林兰意, 项晓刚, 卢捷, 王芃, 莫瑞东, 刘昱含, 蔡伟, 王晖, 谢青. 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[J]. 肝脏, 2016, 21(4): 267-272.

JIANG Shao-wen, LIN Lan-yi, XIANG Xiao-gang, LU Jie, WANG Fan, MO Rui-dong, LIU Yu-han, CAI Wei, WANG Hui, XIE Qing. The expression profiles and significance of IL-33 and its receptor ST2 in a murine model of D-GalN/LPS -induced acute liver failure[J]. Chinese Hepatolgy, 2016, 21(4): 267-272.

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