MHV-3诱导的暴发性肝炎小鼠肝脏和慢加急性肝衰竭患者外周血单个核细胞TLR2表达的变化*

doi:10.3969/j.issn.1672-5069.2014.03.011

实用肝脏病杂志 ›› 2014, Vol. 17 ›› Issue (3): 263-267.doi: 10.3969/j.issn.1672-5069.2014.03.011

MHV-3诱导的暴发性肝炎小鼠肝脏和慢加急性肝衰竭患者外周血单个核细胞TLR2表达的变化^*

李咏, 韩梅芳, 师爱超, 丁琳, 陆玉蕾, 张元亚, 王宏艳, 宁琴

430030 武汉市华中科技大学同济医学院附属同济医院感染性疾病研究所/感染病科（李咏,韩梅芳,师爱超, 丁琳,张元亚,王宏艳）; 广西医科大学附属肿瘤医院（陆玉蕾）

收稿日期:2014-01-24 出版日期:2014-06-30 发布日期:2016-04-11
通讯作者: 宁琴,E-mail:qning@vip.sina.com
作者简介:李咏,男,32岁,博士研究生。主要从事病毒性肝炎发病机制研究。E-mail:vamos_yong@hotmail.com
基金资助:
教育部创新团队项目（编号：IRT1131）

TLR2 in liver tissues of mice with MHV-3-induced fulminant hepatitis and in peripheral blood mononuclear cells from patients with hepatitis B virus associated acute-on-chronic liver failure

Li Yong, Han Meifang, Shi Aichao

Department and Institute of Infectious Disease,Tongji Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan,400030,Hubei Province,China

Received:2014-01-24 Online:2014-06-30 Published:2016-04-11

摘要/Abstract

摘要： 目的研究慢性乙型肝炎患者和慢加急性乙型肝炎肝衰竭（HBV-ACLF）患者外周血单个核细胞（PBMC）Toll样受体2 （TLR2）表达,以及鼠三型肝炎病毒（MHV-3）诱导的暴发性肝炎小鼠肝脏TLR2表达的变化。方法收集慢性乙型肝炎和HBV-ACLF患者外周血,分离PBMC,采用实时定量PCR法检测PBMC中TLR2 mRNA;给Balb/cJ小鼠腹腔注射MHV-3（100 pfu）,建立小鼠暴发性肝炎模型,观察感染0、24、48和72 h后肝脏TLR2水平变化。结果BALB/cJ小鼠在感染MHV-3后,与0 h[（0.39±0.06） %]比,肝细胞TLR2 mRNA水平在感染48和72 h均显著升高[分别为（9.06±1.60） %和（6.42±2.42） %,P<0.05）],并于48 h达最高水平,且两时间点细胞TLR2 mRNA水平均与血清ALT和AST水平呈正相关（r=0.804,P<0.01;r=0.797,P<0.01）;HBV-ACLF患者PBMC 中TLR2 mRNA水平显著高于慢性乙型肝炎患者[（5.92±5.26） % 对（1.15±1.59） %,P<0.05）]。结论TLR2参与了MHV-3诱导的暴发性肝炎小鼠以及HBV-ACLF患者肝脏损伤的发病过程。

关键词: 暴发性肝炎, 慢加急性肝衰竭, 鼠三型肝炎病毒, Toll样受体2, 小鼠

Abstract: Objective To investigate the toll-like receptor 2 （TLR2） in livers of mice with murine hepatitis virus-3 （MHV-3）-induced fulminant hepatitis and in peripheral blood mononuclear cell （PBMCs） from patients with mild chronic hepatitis B（CHB）or with HBV-associated acute-on-chronic liver failure （HBV-ACLF）. Methods PBMCs from patients with mild CHB and HBV-ACLF were collected. The TLR2 mRNA in PBMCs were determined by quantitative real-time PCR. Balb/cJ mice were injected intraperitoneally with MHV-3 at dose of 100 pfu to induce fulminant hepatitis. At 0,24,48 and 72 h after injection,the TLR2 mRNA in liver tissues of mice were determined. Results After infection of MHV-3,TLR2 mRNA increased significantly at 48 and 72 h when compared with the baseline at 0 h [（0.39±0.06）% vs.（9.06±1.60）%,P<0.05 and （6.42±2.42）%,P<0.05] and it peaked at 48 h;mRNA levels for TLR2 at 48 and 72 h were positively correlated with the serum ALT and AST（r=0.804,P<0.01;r=0.797,P<0.01,respectively）;mRNA level of TLR2 in PBMCs from patients with HBV-ACLF was significantly higher than patients with mild CHB [（5.92±5.26）% vs.（1.15±1.59）%,P<0.05]. Conclusions TLR2 may take part in the process of liver injury in MHV-3-induced fulminant hepatitis in mice and the pathogenesis of patients with HBV-ACLF.

Key words: Fulminant hepatitis, Acute-on-chronic liver failure, Murine hepatitis virus-3, Toll-like receptor 2, Mouse

李咏, 韩梅芳, 师爱超, 丁琳, 陆玉蕾, 张元亚, 王宏艳, 宁琴. MHV-3诱导的暴发性肝炎小鼠肝脏和慢加急性肝衰竭患者外周血单个核细胞TLR2表达的变化^*[J]. 实用肝脏病杂志, 2014, 17(3): 263-267.

Li Yong, Han Meifang, Shi Aichao. TLR2 in liver tissues of mice with MHV-3-induced fulminant hepatitis and in peripheral blood mononuclear cells from patients with hepatitis B virus associated acute-on-chronic liver failure[J]. JOURNAL OF PRACTICAL HEPATOLOGY, 2014, 17(3): 263-267.

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MHV-3诱导的暴发性肝炎小鼠肝脏和慢加急性肝衰竭患者外周血单个核细胞TLR2表达的变化^*

TLR2 in liver tissues of mice with MHV-3-induced fulminant hepatitis and in peripheral blood mononuclear cells from patients with hepatitis B virus associated acute-on-chronic liver failure

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