恩替卡韦对慢性乙型肝炎患者CD4＋CD25＋调节性T细胞水平的影响及意义

摘要

Objective:To observe the effect of entecavir on the expression level of CD4+CD25+regulatory T cells(CD4+CD25+Treg) in patients with chronic hepatitis B(CHB), thus to explore the role of CD4+CD25+Treg in the immune pathogenesis of CHB and the effect of entecavir antiviral treatment on the body ’s immunity. Methods: Flow cytometry was used to detect the expressions of CD4+CD25+Treg in 46 patients with CHB before and after the treatment. Real-time fluorescence quantitative ploymerase chain reaction(RT-PCR) was used to detect HBV DNA loads in serum. Enzyme-linked immunoabsorbent assay (ELISA) was adopted to detect the level of transforming growth factor-β1(TGF-β1). Results:The expression level of CD4+CD25+Treg was(4.92±0.49)% before the therapy, which was obviously higher than that in normal control group(2.78±0.41)%(P<0.01). While after the treatment,the level of CD4+CD25+Treg in CHB was decreased to (3.13±0.52)%(P<0.01). CD4+CD25+Treg was positively correlated with HBV DNA loads(r=0.94, P<0.05). And the level of TGF-β1(39.27±5.67) ng/L was significantly decreased compared with that before treatment(21.12±4.66) ng/L(P<0.05). Conclusion: Antiviral treatment with entecavir can decrease viral load, reduce level of CD4+CD25+Treg and TGF-β1, resulting in recovery of immune function, which is beneficial to the removal of hepatitis B virus.%目的：观察恩替卡韦治疗前后，慢性乙型肝炎患者外周血清 C D4＋CD25＋调节性 T 细胞( CD4＋CD25＋regulatory T cells, CD4＋CD25＋Treg)表达水平的变化，揭示CD4＋CD25＋Treg在慢性乙型肝炎免疫发病机制中的作用，及恩替卡韦抗病毒治疗对机体的免疫调节作用。方法：采用流式细胞术检测46例慢性乙型肝炎患者恩替卡韦治疗前、后外周血CD4＋CD25＋Treg的水平；采用实时荧光聚合酶链式反应(real-time fluorescence quantitative ploymerase chain reaction, RT-PCR)检测相应时间点的血清乙型肝炎病毒脱氧核糖核酸(hepatitis B virus DNA, HBV DNA)载量；采用酶联免疫吸附法(enzyme-linked immunoabsorbent assay, ELISA)检测治疗前、后的转化生长因子-β1(transforming growth factor-β1, TGF-β1)水平。结果：慢性乙型肝炎患者外周血清CD4＋CD25＋Treg治疗前为(4.92±0.49)%，明显高于正常对照组的(2.78±0.41)%(P＜0.01)；治疗后CD4＋CD25＋Treg为(3.13±0.52)%，与治疗前相比明显下降(P＜0.01)。 CD4＋CD25＋Treg 水平与HBV DNA 载量呈正相关(r＝0.94, P＜0.05)。治疗后TGF-β1水平(21.12±4.66) ng/L 较治疗前(39.27±5.67) ng/L 明显下降(P＜0.05)。结论：慢性乙型肝炎患者使用恩替卡韦抗病毒治疗后，HBV DNA载量下降，CD4＋CD25＋Treg下降，TGF-β1水平下调，提高了机体的免疫功能，进一步加强了对乙肝病毒的清除。