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

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。

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

Objective To investigate the toll-like receptor 2 （TLR2） in livers of mice with murine hepati-tis virus-3 （MHV-3）-induced fulminant hepatitis and in peripheral blood mononuclear cell （PBMCs） from pa-tients 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-A-CLF was significantly higher than patients with mild CHB （5.92±5.26）% vs.（1.15±1.59）%,P〈0.05]. Conclu-sions 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.