CAJ | 학술논문

目的观察慢性乙型肝炎(CHB)患者应用核苷(酸)类似物(NA)抗病毒治疗前后外周血中Treg、Th17细胞及其相关细胞因子水平的变化.方法采用流式细胞术,检测44例NA治疗12周的CHB患者外周血Treg(CD4+ CD25high CD127low)和Th17(CD3+ CD8-IL-17+)细胞频率.ELISA检测血清IL-10、TGF-β1、IL-17及IL-23水平.各组间采用Mann-Whitney U检验,治疗前后采用Wilcoxon配对T检验.结果完全应答的14例患者的Treg细胞频率、IL-10、TGF-β1和IL-23水平及Treg/Th17比率较治疗前明显下降(Z=-2.691,-2.417,-2.237,-2.291,-2.291,P均＜0.05),Th17细胞频率及IL-17水平略有增加.部分应答的11例患者的Treg细胞频率、IL-10、TGF-β1和IL-23水平较治疗前明显下降(Z=-1.988,-2.934,-2.756,-2.803,P均＜0.05),Th17细胞频率及IL-17水平略有增加,Treg/Th 17比率略有下降.无应答的15例患者的Treg和Th17细胞频率、IL-10、TGF-β1、IL-23、IL-17水平及Treg/Th17比率较治疗无明显变化.HBV DNA下降≥2 log拷贝/ml及ALT恢复正常时,Treg细胞频率与细胞因子IL-10、TGF-β1和IL-23水平较治疗前明显下降(P均＜0.05).Treg细胞频率与HBV DNA及ALT水平三者之间具有一定的相关性.结论 NA抗病毒治疗前后,CHB患者Treg和Th17细胞频率及IL-10、TGF-β1、IL-23、IL-17水平均发生变化；治疗后获得满意应答的CHB患者Treg细胞频率、IL-10、TGF-β1、IL-23水平及Treg/Th17比率明显下降,Th17细胞及IL-17水平继续上升；且以上变化与病毒学应答及生化学应答有关.
목적 관찰만성을형간염(CHB)환자응용핵감(산)유사물(NA)항병독치료전후외주혈중Treg、Th17세포급기상관세포인자수평적변화.방법 채용류식세포술,검측44례NA치료12주적CHB환자외주혈Treg(CD4+ CD25high CD127low)화Th17(CD3+ CD8-IL-17+)세포빈솔.ELISA검측혈청IL-10、TGF-β1、IL-17급IL-23수평.각조간채용Mann-Whitney U검험,치료전후채용Wilcoxon배대T검험.결과 완전응답적14례환자적Treg세포빈솔、IL-10、TGF-β1화IL-23수평급Treg/Th17비솔교치료전명현하강(Z=-2.691,-2.417,-2.237,-2.291,-2.291,P균＜0.05),Th17세포빈솔급IL-17수평략유증가.부분응답적11례환자적Treg세포빈솔、IL-10、TGF-β1화IL-23수평교치료전명현하강(Z=-1.988,-2.934,-2.756,-2.803,P균＜0.05),Th17세포빈솔급IL-17수평략유증가,Treg/Th 17비솔략유하강.무응답적15례환자적Treg화Th17세포빈솔、IL-10、TGF-β1、IL-23、IL-17수평급Treg/Th17비솔교치료무명현변화.HBV DNA하강≥2 log고패/ml급ALT회복정상시,Treg세포빈솔여세포인자IL-10、TGF-β1화IL-23수평교치료전명현하강(P균＜0.05).Treg세포빈솔여HBV DNA급ALT수평삼자지간구유일정적상관성.결론 NA항병독치료전후,CHB환자Treg화Th17세포빈솔급IL-10、TGF-β1、IL-23、IL-17수평균발생변화；치료후획득만의응답적CHB환자Treg세포빈솔、IL-10、TGF-β1、IL-23수평급Treg/Th17비솔명현하강,Th17세포급IL-17수평계속상승；차이상변화여병독학응답급생화학응답유관.
Objective To explore the relationship between the efficacy of nucleos(t) ide analogues antivirus therapy and changes of Treg cells,Th17 cells and their associated cytokines in the peripheral blood of patients with CHB.Methods Forty-four CHB patients treated for 12 weeks were enrolled in this study.The frequencies of Treg ceils (CD4+CD25highCD127low T cells) and Th17 cells (CD3+CD8-IL-17+ T cells)in the peripheral blood were assessed by flow cytometric analysis.Treg/Th17 cell-associated cytokines IL-10,TGF-β1,IL-17 and IL-23 levels were measured by enzyme-linked immunosorbent assay (ELISA).The comparisons of overall means within groups and between before and after therapy were done by Mann-Whitney U test or Wilcoxon matched paired T test.Results In 14 complete-responders of 44 CHB patients,the frequencies of Treg cells,the levels of IL-10,TGF-β1 and IL-23 and Treg/Th17 ratio were decreased significantly after nucleos(t) ide analogues antivirus therapy (Z=-2.691,-2.417,-2.237,-2.291,-2.291,both P＜0.05),while the frequencies of Th17 cells and the IL-17 levels were increased slightly.In 11 patrial-responders,the frequencies of Treg cells,the levels of IL-10,TGF-β1 and IL-23 were decreased significantly after nucleos(t)ide analogues antivirus therapy (Z=-1.988,-2.934,-2.756,-2.803,both P＜0.05) ; The frequencies of Th17 cells and the IL-17 levels were increased slightly,while Treg/Th17 ratio was slightly decreased.In 15 non-responders,the frequencies of Treg cells,Th17 cells,the levels of IL-10,TGF-β1,IL-17 and IL-23 and Treg/Th17 ratio were not changed significantly after nucleos(t)ide analogues antivirus treatment.Either HBV DNA decrease at least 2 log copies/ml or ALT normal,the frequencies of Treg cells,the levels of IL-10,TGF-β1 and IL-23 were decreased significantly (all P＜0.05).The frequencies of Treg cells were positively correlated with HBV DNA and ALT,and the level of HBV DNA were correlated with ALT.Conclusion Treg and Th17 cells and their associated cytokines were changed significantly before and after NA treatment.In CHB patients who have achieved response after NA therapy,the frequency of Treg cells,the levels of IL-10,TGF-β1 and IL-23 and Treg/Th17 ratio in the peripheral blood were decreased,while Th17 cells frequencies and IL-17 levels were increased.