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干扰素治疗对慢性乙型肝炎患者外周血单个核细胞端粒酶活性表达的影响
Impact of interferon-α therapy on expression of telomerase activity in peripheral blood mononuclear cells in patients with chronic hepatitis B
【摘要】 目的探讨干扰素抗病毒治疗对慢性乙型肝炎(CHB)患者外周血单个核细胞(PBMCs)端粒酶逆转录酶活性表达的影响。方法用淋巴细胞分离液分离37例干扰素治疗CHB患者(干扰素治疗组),36例CHB对照患者(患者对照组)和10例健康人(健康对照组)的PBMCs,用Real-time RT-PCR方法定量检测各组PBMCs表达的hTERT mRNA及其相应β-actin mRNA,计算出标化的hTERT mRNA(NhTERT mRNA)。结果干扰素治疗12个月时,治疗组PBMCs表达NhTERT mRNA的水平与正常对照组之间无统计学差异,但两组均显著高于患者对照组(P<0.001;P=0.001)。hTERT mRNA的水平与研究对象的年龄、患者基线ALT水平、HBV DNA载量及病毒基因型等均未见显著相关性关系(均为P>0.05),但治疗12个月时,其水平与同期检测的CD3+T淋巴细胞计数、CD4+/CD8+比值均呈显著正相关关系(P<0.05)。并且发现,在干扰素治疗组中NhTERT mRNA的表达随治疗时间的延长而显著增加,在治疗12个月时获得完全应答的患者组NhTERT mRNA水平显著高于无应答组(P<0.05)。结论 CHB患者PBMCs端粒酶活性表达低下,干扰素抗病毒治疗可以上调患者淋巴细胞端粒酶活性,这可能是干扰素促进患者免疫功能恢复的一种机制。
【Abstract】 Objective To investigate the impact of interferon alpha(IFNα) antiviral therapy on the expression of telomerase activity in peripheral blood mononuclear cells(PBMCs) in patients with chronic hepatitis B(CHB). Methods PBMCs were obtained from 37 CHB patients treated with IFNα(IFNα treated group), 36 CHB control patients(CHB control group) and 10 healthy individuals(healthy control group). The quantitation of hTERT mRNA and β-actin mRNA in PBMCs was respectively detected by real-time RT-PCR, and the normalized hTERT mRNA(NhTERT mRNA) was calculated for each sample. Results NhTERT mRNA level at 12 months of IFNα treatment was similar to that in healthy control group, but all were significantly higher than that in CHB control group(P<0.001 and P=0.001, respectively). The expression of NhTERT mRNA was not significantly correlated with subject’s age, patient’s baseline alanine aminotransferase, HBV DNA load and HBV genotypes, respectively(all P>0.05), but the level at 12 months of IFNα treatment was significantly correlated with the count of CD3+ T lymphocytes(P=0.001) and the ratio of CD4+/CD8+ lymphocytes(P=0.009) detected during the same period in IFNα treated group. In addition, the mean level was found to be significantly increased with treatment time, and the mean level at 12 months of IFNα treatment in complete response subgroup was remarkably higher than that in non-complete response subgroup(P<0.05) in IFNα treated group. Conclusion A decreased telomerase activity is expressed in PBMCs of CHB patients, and IFNα therapy can up-regulate its expression, which may be a kind of mechanism for IFNα to improve patient’s immune function.
【Key words】 Hepatitis B,chronic; Interferon alpha; Peripheral blood mononuclear cell; Human telomerase reverse transcriptase;
- 【文献出处】 中华临床医师杂志(电子版) ,Chinese Journal of Clinicians(Electronic Edition) , 编辑部邮箱 ,2013年23期
- 【分类号】R512.62
- 【下载频次】37