2',5'-寡腺苷酸合成酶基础活性对干扰素α治疗慢性丙型肝炎信号传导的影响机制研究  

Study on the mechanism of the basal 2',5'-oligoadenylate synthetase activity on interferon alpha signal transduction in patients with chronic hepatitis C

作　　者：苏冬娜[1,2] 陈洪涛[1,2] 

机构地区：[1]深圳市人民医院 [2]暨南大学第二临床学院感染内科,广东深圳518020

出　　处：《新乡医学院学报》2015年第7期638-641,共4页Journal of Xinxiang Medical University

基　　金：深圳市卫生计生系统科研项目(编号:201402004)

摘　　要：目的观察慢性丙型肝炎患者外周血单个核细胞(PBMC)中2',5'-寡腺苷酸合成酶(2-5AS)基础活性对干扰素(IFN)信号分子改变的影响,探讨IFN-α治疗慢性丙型肝炎的作用机制。方法选择60例慢性丙型肝炎患者,抽取外周血分离出PBMC,每份标本进行2-5AS基础活性测定后分为实验组和对照组,对照组PBMC体外培养时不加IFN-α,实验组PBMC体外培养时加入IFN-α。培养24 h后,测定PBMC中2-5AS活性、IFN-α受体(IFN-αR)、信号传导及转录激活因子(Stat)1、Stat2、两面神激酶1(Jak1)和酪氨酸激酶2(Tyk2)等指标。结果实验组PBMC培养24 h后2-5AS活性、Jak1、Stat1、Stat2和Tyk2等表达明显增高(P<0.05),IFN-αR表达降低(P<0.05)。2-5AS基础活性与IFN-α刺激下PBMC中2-5AS、Tyk2和Stat1的表达呈负相关(P<0.05),而与IFN-αR、Jak1和Stat2的表达无相关性(P>0.05)。结论 2-5AS基础活性可下调PBMC对外源性IFN-α的敏感性,Stat1、Tyk2表达降低可能是下调机制发生的原因。Objective To study the mechanism of interferon alpha（ IFN-α） for treating chronic hepatitis C by observing the effect of the basal activity of 2＇,5＇-oligoadenylate synthetase on the IFN signaling molecules changes in peripheral blood mononuclear cell（ PBMC） of patients with chronic hepatitis C. Methods The PBMC were isolated from peripheral blood of 60 patients with chronic hepatitis C,each sample was divided into experiment group and control group after determination of basal2-5AS activity. The PBMC in control group were cultivated in vitro without IFN-α interference,but the PBMC in experiment group were cultivated in vitro with IFN-α interference. Twenty-four hours after cultivation,the levels of 2-5AS activity,IFN-αreceptor（ IFN-αR）,Janus kinase 1（ Jak1）,signal transducers and activators of transcription（ Stat） 1,Stat2,Tyk2 in PBMC were detected. Results Twenty-four hours after cultivation,2-5AS activity and Jak1,Stat1,Stat2,Tyk2 expression increased significantly（ P〈0. 05）,but the expression of IFN-αR decreased in experiment group（ P〈0. 05）. The basal activity of 2-5AS was negatively correlated with 2-5AS level,Tyk2 and Stat1 expression in PBMC after IFN-α stimulation（ P〈0. 05）. But there was no correlation between the basal activity of 2-5AS and IFN-αR,Jak1 or Stat2 expression（ P〈0. 05）. Conclusions The basal activity of 2-5AS may down regulate the sensitivity of PBMC to exogenous IFN-α. The decreased expression of Stat1 and Tyk2 may be the reason for the downregulation.

关 键 词：2' 5'-寡腺苷酸合成酶 干扰素 慢性丙型肝炎 信号分子 

分 类 号：R512.6[医药卫生—内科学]