摘要
目的研究恩替卡韦(ETV)治疗48周过程中慢性乙型肝炎患者外周血单个核细胞(PMBCs)中Th1及Th2类细胞的变化,为新的免疫治疗探索方向。方法 2008年11月-2009年11月于解放军302医院门诊诊断为慢性乙型肝炎的患者9例,列入HBV感染组;另选择9名健康对照者作为健康对照组。HBV感染组患者在应用ETV治疗的开始及第4、12、24、36、48周时取静脉血,分离血清及PMBCs,检测血清中乙型肝炎病毒(HBV)表面标志物(HBV-M)、HBV核酸定量(HBV-DNA)及丙氨酸转移酶(ALT)水平;行细胞内细胞因子染色,应用FACSCalibur流式细胞仪检测PMBCs中Th1及Th2类细胞频数,并用FACSCalibur软件进行分析。结果应用ETV治疗后HBV感染组患者ALT水平及HBVDNA从第4周开始出现明显下降,至第48周时与健康对照组无明显差异;表型为CD3+CD4+IFN-γ+的Th1类细胞的频数在第4周时明显升高,其后逐渐下降,在第48周时接近低于基线点,但高于健康对照组。表型为CD3+CD4+IL-4+的Th2细胞的频数明显升高,在第12周时达到峰值,其后明显下降,明显低于健康对照组。结论 ETV在有效抑制病毒复制的同时,体内Th1类免疫反应下降而Th2类免疫反应不足,提示体内炎症反应减轻,但同时机体清除病毒的能力也被削弱。
Objective To investigate the change in feature of Th1and Th2cells in the peripheral blood mononuclear cells（PBMCs） of CHB patients during 48weeks of treatment period with enticarvir（ETV）,and find the new immune therapy methods.Methods Nine CHB patients（HBV-infected group）diagnosed in 302Hospital of PLA from Nov.2008to Nov.2009,and 9healthy volunteers as control,were enrolled.Serum and PBMCs were obtained from patients in HBV-infected group at the baseline point and 4th,12th,24th, 36th and 48th week during the ETV treatment.HBV markers（HBV-M）,HBV DNA and ALT levels in serum were determined. FACSCalibur flow cytometry was performed to detect the cell frequency of Th1and Th2in PMBCs after the intracellular cytokine staining. FACSCalibur software was used to analyze the results.Results There was a significant decrease in ALT and HBV DNA levels in CHB patients at 4th week after ETV treatment.No significant difference was found between CHB patients and healthy controls at 48th week. The frequency of CD3^＋CD4^＋IFN-γ^＋cells significantly increased at 4th week and gradually decreased later.Until the 48th week,it decreased to approach the baseline,while still higher than that of the counterparts in healthy controls.The frequency of CD3^＋CD4^＋IL-4^＋ cells significantly increased and reached the peak value at 12th week,then decreased and was significantly lower than that in controls at any time point.Conclusion The suppression of HBV replication by ETV may lead to the decrease of Th1immune reaction and insufficiency of Th2immune reaction,which may attenuate the hepatic inflammation and weaken the ability of virus clearing.
出处
《解放军医学杂志》
CAS
CSCD
北大核心
2010年第12期1465-1467,共3页
Medical Journal of Chinese People's Liberation Army
关键词
抗病毒药
肝炎病毒
乙型
免疫
细胞
antiviral agents； hepatitis B virus； immunity,cellular
