中华肝脏病杂志
中華肝髒病雜誌
중화간장병잡지
CHINESE JOURNAL OF HEPATOLOGY
2010年
4期
263-266
,共4页
肝炎病毒,乙型%流体动力学%PD-1/PD-L1%信号通路
肝炎病毒,乙型%流體動力學%PD-1/PD-L1%信號通路
간염병독,을형%류체동역학%PD-1/PD-L1%신호통로
Hepatitis B virus%Hydrodynamics%PD-1/PD-L1%Signaling pathway
目的 建立慢性HBV感染的小鼠模型,体内阻断PD-1/PD-L1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/HBV1.2-GFP,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PD-L1的单克隆抗体,检测小鼠血清ALT和HBV DNA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90 d后仍能检测到血清HBsAg的表达及高载量的HBV DNA.体内阻断PD-1/PD-L1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HBV DNA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PD-1/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.
目的 建立慢性HBV感染的小鼠模型,體內阻斷PD-1/PD-L1信號通路,增彊模型小鼠的抗病毒免疫,探尋慢性乙型肝炎治療的新方法.方法 以流體動力學法給C57BL/6小鼠尾靜脈註射pAAV/HBV1.2-GFP,不同時間點檢測血清和組織中各種HBV標誌物的錶達.給模型小鼠腹腔註射抗PD-L1的單剋隆抗體,檢測小鼠血清ALT和HBV DNA載量的變化.兩計量資料比較採用t檢驗.結果 成功建立慢性HBV感染小鼠模型,建模90 d後仍能檢測到血清HBsAg的錶達及高載量的HBV DNA.體內阻斷PD-1/PD-L1信號通路後,小鼠血清ALT水平明顯上升(t=5.436,P＜0.01),同時,血清HBV DNA載量顯著下降,t=4.919,P＜0.01,差異有統計學意義.結論 慢性HBV感染小鼠模型是研究HBV感染免疫耐受機製及治療方法較好的工具;體內阻斷PD-1/PD-L1信號通路,能增彊慢性HBV感染小鼠的抗病毒免疫,可能成為慢性乙型肝炎治療的新策略.
목적 건립만성HBV감염적소서모형,체내조단PD-1/PD-L1신호통로,증강모형소서적항병독면역,탐심만성을형간염치료적신방법.방법 이류체동역학법급C57BL/6소서미정맥주사pAAV/HBV1.2-GFP,불동시간점검측혈청화조직중각충HBV표지물적표체.급모형소서복강주사항PD-L1적단극륭항체,검측소서혈청ALT화HBV DNA재량적변화.량계량자료비교채용t검험.결과 성공건립만성HBV감염소서모형,건모90 d후잉능검측도혈청HBsAg적표체급고재량적HBV DNA.체내조단PD-1/PD-L1신호통로후,소서혈청ALT수평명현상승(t=5.436,P＜0.01),동시,혈청HBV DNA재량현저하강,t=4.919,P＜0.01,차이유통계학의의.결론 만성HBV감염소서모형시연구HBV감염면역내수궤제급치료방법교호적공구;체내조단PD-1/PD-L1신호통로,능증강만성HBV감염소서적항병독면역,가능성위만성을형간염치료적신책략.
Objective To establish a mouse model for human chronic HBV infection,and to investigate the role ofPD-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 sernm 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.
