CAJ | 학술논문

目的：探索核苷类药物替比夫定的免疫调节作用。方法选择6～8周健康雄性BALB／c小鼠，每日灌胃替比夫定，对照组每日灌胃等量0．9％氯化钠溶液。14 d后取小鼠脾脏细胞，检测记忆性T细胞表型，调节性T细胞比例，T细胞中IL‐2、TNF‐α及IFN‐γ表达水平，并以羟基荧光素二醋酸盐琥珀酰亚胺脂（CFSE）染色法检测 T 细胞的增殖能力。结果与对照组相比，替比夫定灌胃组小鼠脾脏中T细胞分泌细胞因子IL‐2、TNF‐α及IFN‐γ的水平，和由 TCR／CD3作用下的细胞增殖能力均无显著性差异，但脾脏T细胞的亚群分布发生明显改变，初始T细胞比例明显升高，效应T细胞比例明显降低，且调节性T细胞的比例也明显降低。结论替比夫定导致的外周初始T细胞的比例升高和调节性T细胞比例的降低有利于增强免疫系统对外界抗原的应答能力，替比夫定不仅可以通过直接抑制病毒复制发挥药效，同时还有可能通过调节患者的免疫功能发挥间接抗病毒作用。
목적：탐색핵감류약물체비부정적면역조절작용。방법선택6～8주건강웅성BALB／c소서，매일관위체비부정，대조조매일관위등량0．9％록화납용액。14 d후취소서비장세포，검측기억성T세포표형，조절성T세포비례，T세포중IL‐2、TNF‐α급IFN‐γ표체수평，병이간기형광소이작산염호박선아알지（CFSE）염색법검측 T 세포적증식능력。결과여대조조상비，체비부정관위조소서비장중T세포분비세포인자IL‐2、TNF‐α급IFN‐γ적수평，화유 TCR／CD3작용하적세포증식능력균무현저성차이，단비장T세포적아군분포발생명현개변，초시T세포비례명현승고，효응T세포비례명현강저，차조절성T세포적비례야명현강저。결론체비부정도치적외주초시T세포적비례승고화조절성T세포비례적강저유리우증강면역계통대외계항원적응답능력，체비부정불부가이통과직접억제병독복제발휘약효，동시환유가능통과조절환자적면역공능발휘간접항병독작용。
Objective To investigate the immunomodulatory effect of nucleotide anologues (telbivudine) .Methods Healthy male BALB/c mice of 6‐8 weeks old were given a gavage of telbivudine for 14 days as experimental group ,while mice were given a gavage of saline of the same volume with the drug as control group .Mice were sacrificed for analysis of memory T cells subset distribution ,regulatory T cells population in spleen ,and levels of interleukin‐2 (IL‐2) ,tumor necrosis factor‐α (TNF‐α) ,interferon‐γ (IFN‐γ) secreted from T cells by flow cytometry .The proliferation of T cells in spleen was detected by 5 ,6‐carboxyfluorescein diacetate succinimidyl ester (CFSE) staining .Results When compared to those in control group ,cytokine profiling of IL‐2 ,TNF‐α,IFN‐γand proliferation of T cells in spleen ,which stimulated by T cell receptor (TCR)/CD3 ,showed no significant difference in experimental group .However ,compared with those in control group ,T cells subset distribution in spleen in experimental group showed obviously changed ,such as significant increase of naive T cells frequency and significant dicrease of effector/memory and regulatory T cells . Conclusion Stimulated by telbivudine ,up‐regulation of peripheral naive T cells and down‐regulation of regulatory T cells might enhance immune responses to external antigens .Thus long‐term treatment with telbivudine might play dual roles in chronic hepatitis B through directly viral inhibition and indirectly immunomodulatory effect .