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。
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.