环孢素A和他克莫司在体外对外周血单个核细胞内乙型肝炎病毒复制的影响

In vitro effect of ciclosporin A and tacrolimus on the replication of peripheral blood mononuclear cells mesne hepatitis B virus

目的:探讨环孢素A(ciclosporin A, CsA)和他克莫司(FK506)在体外对外周血单个核细胞内乙型肝炎病毒复制的影响。方法:建立乙型肝炎病毒脱氧核糖核酸(HBV-DNA)永久转染人外周血单个核细胞株,计算CsA和FK506对HBV-DNA永久转染人外周血单个核细胞株的药物安全浓度,采用狭缝印迹杂交法半定量分析细胞内HBVDNA水平。结果:CsA和FK506的药物作用安全浓度分别是≤36μg/ml和≤200 ng/ml。在安全浓度范围内,CsA的质量浓度与细胞内HBV-DNA相对复制水平呈显著负相关(r=-0.886,P <0.05);FK506的质量浓度与细胞内HBVDNA相对复制水平无明显相关性(r=-0.593,P>0.05)。结论:CsA在体外呈剂量依赖性地抑制外周血单个核细胞内乙型肝炎病毒复制,而FK506不具备上述特性。

Objective:To discuss the effect of ciclosporin A(CsA)and tacrolimus(FK506)on the replication of peripheral blood mononuclear cells mesne hepatitis B virus in vitro.Methods:A human peripheral blood mononuclear cell line permanently transfected with hepatitis B virus deoxyribonucleic acid(HBV-DNA)was established to calculate the safe concentrations of CsA and FK506 for HBV-DNA permanently transfected human peripheral blood mononuclear cell line,and semi-quantitative analysis of intracellular HBV-DNA levels was performed by slot blot hybridization.Results:The safe concentrations of CsA and FK506 were<36 mg/ml and<200 ng/ml,respectively.Within the safe concentration range,the mass concentration of CsA was negatively correlated with the relative replication level of HBV-DNA in cells(r=-0.886,P<0.05);the mass concentration of FK506 was not correlated with the relative replication level of HBV-DNA in cells(r=-0.593,P>0.05).Conclusion:CsA can in vitro inhibit hepatitis B virus replication in peripheral blood mononuclear cells in a dose-dependent manner but not FK506.