抑制性寡脱氧核苷酸对肝损伤小鼠pSTAT4、pSTAT6和T-bet表达的影响及其意义

The effect of suppressive oligodeoxynucleotide on pSTAT4,pSTAT6 and Tbet expression of concanavalin A-induced liver injury in micee

目的探讨抑制性寡脱氧核苷酸(suppressive oligodeoxynucleotide,Sup ODN)对刀豆蛋白A(ConA)诱导肝损伤小鼠兔抗鼠磷酸化信号转导和转录激动子4抗体(pSTAT4)、pSTAT6和T-bet表达的影响及其意义。方法 Balb/C小鼠40只被随机分为4组,分别为生理盐水(NS,空白对照)组、环孢菌素A(CsA)组(阳性对照)、Con ODN组(对照ODN)、Sup ODN组(实验组)。ConA(20mg/kg)尾静脉注射Balb/C小鼠造模,造模同时分别给予Sup ODN、Con ODN、CsA或NS 0.3 mL腹腔注射,分别于干预后8 h和24 h摘取小鼠脾脏,提取蛋白检测pSTAT4、pSTAT6和T-bet的表达。结果无论是干预后8 h还是24 h,Sup ODN组pSTAT4及T-bet蛋白的表达水平与NS、Con ODN及CsA组相比,均显著下降(均P<0.01);而pSTAT6蛋白表达水平,Sup ODN组与NS、Con ODN及CsA组差异均无显著性(均P>0.05)。结论 Sup ODN可能通过抑制细胞内转录因子pSTAT4和T-bet的表达,抑制小鼠Th1型免疫应答,最终实现其对肝损伤的保护作用。

Objective To investigate the effect of suppressive oligodeoxynucleotide （Sup ODN） on pSTAT4, pSTAT6 and T-bet expression of concanavalin A induced liver injury in mice. Methods Forty Balb/C mice were randomly divided into 4 groups, normal saline group （NS, blank control group）, cyclosporin A group （CsA group, positive control group） , control oligodeoxynucleotide group （control ODN group）, and Sup ODN group （trial group）. Mice in each group were injected with ConA（20mg/kg） via the tail vein to make liver injury model. Sup ODN, Con ODN, CsA or NS was injected intraperitoneally at the same time of ConA injection. The expression of pSTAT4 , pSTAT6 and Tbet in spleen at the 8th or 24th hour after intraperitoneal injection was examined by Western-blotting. Results pSTAT4 and T-bet in Sup ODN group were significantly lower compared with NS, Con ODN or CsA group respectively （ all P〈0. 01 ） ; pSTAT6 had no difference between Sup ODN group and other groups （ all P〈 0. 01 ）. Conclusion Sup ODN attained protective effect on ConA induced mice liver injury by supressing expression of pSTAT4 and Tbet.