阻断程序性死亡蛋白-1及其配体信号通路增强慢性乙型肝炎病毒感染小鼠的抗病毒免疫  

Enhancement of antiviral immunity in HBV mouse model by blocking PD-1/PD-L1 signaling pathway

作　　者：翁志宏[1] 叶翩[1] 张淑玲[1] 

机构地区：[1]华中科技大学同济医学院附属协和医院感染科, 武汉430022

出　　处：《中华肝脏病杂志》2010年第4期263-266,共4页Chinese Journal of Hepatology

摘　　要：目的建立慢性HBV感染的小鼠模型，体内阻断PD1／PDL1信号通路，增强模型小鼠的抗病毒免疫，探寻慢性乙型肝炎治疗的新方法。方法以流体动力学法给C57BL／6小鼠尾静脉注射pAAV／HBV1．2GFP，不同时间点检测血清和组织中各种HBV标志物的表达。给模型小鼠腹腔注射抗PDL1的单克隆抗体，检测小鼠血清ALT和HBVDNA载量的变化。两计量资料比较采用t检验。结果成功建立慢性HBV感染小鼠模型，建模90d后仍能检测到血清HBsAg的表达及高载量的HBVDNA。体内阻断PD1／PDL1信号通路后，小鼠血清ALT水平明显上升（t=5．436，P〈0．01），同时，血清HBVDNA载量显著下降，t=4．919，P〈0．01，差异有统计学意义。结论慢性HBV感染小鼠模型是研究HBV感染免疫耐受机制及治疗方法较好的工具；体内阻断PD1／PD—L1信号通路，能增强慢性HBV感染小鼠的抗病毒免疫，可能成为慢性乙型肝炎治疗的新策略。Objective To establish a mouse model for human chronic HBV infection, and to investigate the role of PD-1/PD-L1 signaling pathway in antiviral immunity. Methods A mouse model was established by hydrodynamic injection of the plasmid pAAV/HBV 1.2-GFP into the tail vein of C57BL/ 6 mice, HBV markers were assayed at different time points after injection. After intraperitoneal injection of anti-PD-L1 monoclonal antibody, the serum ALT, and HBV DNA in the serum, liver and kidney were assayed. Results The chronic HBV infection mouse model were established successfully, serum HBsAg and high load of HBV DNA were detectable 90 days after plasmid injection. After blocking of the PD-1/PD-L1 pathway, the serum ALT level of mice were significantly increased （P 〈 0.01）, and the HBV DNA load in serum （P 〈 0.01）, liver （P 〈 0.05） and kidney （P 〈 0.05） were decreased significantly. Conclusion Blocking the PD-1/PD-L1 signaling pathway can enhance antiviral response in mice with chronic HBV infection.

关 键 词：肝炎病毒 乙型 流体动力学 PD-1/PD-L1 信号通路 

分 类 号：R51[医药卫生—内科学]