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目的研究慢性乙型肝炎(CHB)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α(IFN-α)信号分子改变的影响。探讨IFN-α治疗CHB的作用机理。方法取45例CHB患者外周血,分离出PBMC。一部分用于2-5AS基础活性测定,其余部分分为2组,分别用于不加IFN-α的体外培养(体外基础组)和加1000 IU/ml IFN-α的体外培养(体外诱生组)。两组同时在体外进行细胞培养24h后,测定PBMC中2-5AS活性、IFN-α受体(IFN-αR)表达以及Jak1、Stat1和Stat2的水平。评价2-5AS基础活性与2-5AS、IFN-αR、Jak1、Stat1和Stat2在IFN-α刺激下改变(体外诱生组/体外基础组的比例)的相关性。结果IFN-α体外刺激24h后PBMC中2-5AS、Jak1、Stat1和Stat2水平明显增高(P＜0．05)；IFN-αR的表达降低(P＜0．05)。2-5AS基础活性与IFN-α刺激下2-5AS和Stat1的增长呈负相关(P＜0．05),与IFN-αR、Jak1和Stat2的改变之间没有相关性(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,下调机制可能与Stat1的诱生低下有关。
Objective To study the changes of basic interferon alpha (IFN-α) signaling molecules in basal activity of 2 ’, 5’-oligoadenylate synthase (2-5AS) in peripheral blood mononuclear cells (PBMCs) from patients with chronic hepatitis B Impact. To investigate the mechanism of IFN-α treatment of CHB. Methods 45 cases of CHB patients with peripheral blood, PBMC were isolated. One part was used for basal activity measurement of 2-5AS, and the other part was divided into two groups, which were used for in vitro culture (in vitro basal group) without IFN-α and in vitro culture supplemented with 1000 IU / ml IFN-α ). The two groups were simultaneously cultured in vitro for 24 hours, and the activity of 2-5AS, the expression of IFN-α receptor (IFN-αR) and the levels of Jak1, Stat1 and Stat2 in PBMC were measured. The basal activity of 2-5AS was assessed for the association with 2-5AS, IFN-αR, Jak1, Stat1 and Stat2 changes under stimulation of IFN-α (ratio of in vitro-inducible / basal group in vitro). Results The levels of 2-5AS, Jak1, Stat1 and Stat2 in PBMC were significantly increased (P <0.05) and the expression of IFN-αR was decreased in IFN-α treated group (P <0.05). The basal activity of 2-5AS was negatively correlated with the increase of 2-5AS and Stat1 (P <0.05), but not with the changes of IFN-αR, Jak1 and Stat2 (P> 0.05 ). Conclusion The basal activity of 2-5AS can down-regulate the sensitivity of PBMC to exogenous IFN-α, which may be related to the low induction of Stat1.