HCV感染者直接抗病毒药物治疗对miR-181a调节CD4^(+)T淋巴细胞衰老相关指标的影响  

Regulatory effect of miR-181a on senescence-related indicators of CD4^(+)T lymphocytes in HCV-infected patients before and after direct antiviral agent therapy

作　　者：李瑞娟 权会琴 王晓艳 边培育 叶传涛 范超 张颖 周云 LI Ruijuan;QUAN Huiqin;WANG Xiaoyan;BIAN Peiyu;YE Chuantao;FAN Chao;ZHANG Ying;ZHOU Yun(Department of Infectious Diseases,Tangdu Hospital,Air Force Medical University,Xi'an 710038,China)

机构地区：[1]空军军医大学唐都医院传染科,陕西西安710038

出　　处：《空军军医大学学报》2022年第8期995-1000,共6页Journal of Air Force Medical University

基　　金：国家自然科学基金(81601749,81870414)。

摘　　要：目的研究miR-181a调节丙型肝炎病毒(HCV)感染者直接抗病毒药物(DAA)治疗过程中对CD4^(+)T淋巴细胞衰老相关指标的影响。方法纳入的26例HCV感染者为HCV组;接受索磷布韦联合达卡他韦片治疗达病毒性治愈者22例为HCV治愈组;以及20例健康对照者为健康对照组。采用qRT-PCR方法检测外周血单个核细胞中CD4^(+)T淋巴细胞上miR-181a,SIRT 1、P 53、P 21 mRNA表达水平。双荧光素酶报告基因检测miR-181a-5p对SIRT1的调控作用。采用流式细胞仪检测CD4^(+)T淋巴细胞上SIRT1、CD57、PD-1、TIM-3分子的表达。计量资料多组间比较采用单因素方差分析,进一步两两比较采用Bonferroni法。结果miR-181a、SIRT 1、PD-1、TIM-3表达水平在三组间差异有统计学意义(F=7.59,9.69,5.31,11.33;P<0.01)。与健康对照组相比,HCV组、HCV治愈组CD4^(+)T细胞上miR-181a下降,miR-181a能特异性地抑制SIRT1表达。与健康对照组相比,HCV组CD4^(+)T细胞上SIRT1、PD-1、TIM-3表达上升,经过治疗,HCV治愈组SIRT1、PD-1、TIM-3表达水平下降,但与HCV组无统计学差异。P 53、P 21在三组间表达有差异(F=6.53,27.02;P<0.01)。与健康对照组相比,HCV治愈组和HCV组P53(P<0.05)和P 21水平下降(P<0.01),HCV组和HCV治愈组相比无统计学差异。结论miR-181a通过SIRT 1调节HCV感染者CD4^(+)T细胞衰老,经DAA治疗后,SIRT1、PD-1、TIM-3表达水平下降,提示CD4^(+)T细胞衰老部分缓解。Objective To investigate the effect of miR-181a on senescence-related indicators of CD4^(+)T lymphocytes in hepatitis C virus(HCV)-infected patients during direct antiviral agent(DAA)treatment.Methods The study enrolled 26 untreated patients with chronic hepatitis C in HCV group,22 patients who had received oral sofosbuvir and daclatasvir tablet treatment in HCV treated group,and 20 healthy controls in healthy control group.The expression levels of miR-181a,SIRT1,P53 and P21 mRNA on CD4^(+)T cells in peripheral blood mononuclear cell were detected by qRT-PCR.The regulation of SIRT1 by miR-181a-5p was observed using dual luciferin reporter genes.The expressions of SIRT1,CD57,PD-1,and TIM-3 on CD4^(+)T cells were tested by flow cytometer.One-way ANOVA was used for comparison of normally distributed continuous data among multiple groups,and Bonferroni test was used for further comparison between two groups.Results The expression levels of miR-181a,SIRT 1,PD-1 and TIM-3 mRNA were significantly different in the three groups(F=7.59,9.69,5.31,11.33;P<0.01).Compared with healthy control group,miR-181a on CD4^(+)T cells decreased in HCV group and HCV treated group.MiR-181a could specifically inhibit the expression of SIRT1.Compared with healthy control group,the expressions of SIRT1,PD-1 and TIM-3 on CD4^(+)T cells increased in HCV group.After treatment,the expressions of SIRT1,PD-1 and TIM-3 decreased in HCV treated group,but there was no statistical difference between HCV treated group and HCV group.The expressions of P53 and P21 were significantly different in the three groups(F=6.53,27.02;P<0.01).Meanwhile,the levels of P53(P<0.05)and P21(P<0.01)decreased in HCV treated group and HCV group compared with healthy control group,and there was no significant difference between HCV group and HCV treated group.Conclusion MiR-181a regulates the senescence of CD4^(+)T cells in HCV-infected patients through SIRT1.After DAA treatment,the expressions of SIRT1,PD-1 and TIM-3 decreased,suggesting partial remission of senescence of

关 键 词：丙型肝炎病毒 抗病毒药 CD4^(+)T淋巴细胞 细胞衰老 

分 类 号：R512.63[医药卫生—内科学]