miR155调控TLR9信号通路对溃疡性结肠炎的影响

Effect of miR155 on TLR9 Signaling Pathway in Ulcerative Colitis

目的探讨miR155调控TLR9信号通路对溃疡性结肠炎(ulcerative colitis,UC)的影响。方法采用3%葡聚糖硫酸钠(DSS)饮水的方法构建UC小鼠模型,用ELISA测定小鼠血清CP、IL-6、IL-1β、TNF-α含量,PCR检测miR-155、TLR9、MyD88、NF-kB以及IL-1β、TNF-αmRNA水平,western blot测定TLR9、MyD88、NF-kB蛋白表达水平。结果与正常组小鼠比较,UC模型组小鼠体重明显下降,疾病活动指数(DAI)明显增加,结肠长度显著缩短;此外,UC小鼠炎症因子MPO、CP、IL-6、IL-1β、TNF-α明显升高,miR-155、TLR9、MyD88、NF-kB以及IL-1β、TNF-αmRNA水平显著高于正常小鼠,TLR9、MyD88、NF-kB蛋白表达明显增加。结论miR-155可能通过调控TLR9信号通路参与UC炎症反应,抑制miR-155-TLR9信号通路可能对UC具有保护作用,为UC治疗提供一个潜在靶点。

Objective To investigate the effect of miR155 regulating TLR9 signaling pathway on ulcerative colitis.Methods The UC mouse model was established by using 3%DSS(sodium sulfate)drinking water.Serum CP,IL-6,IL-1βand TNF-αwere determined by ELISA.The mRNA levels of miR-155,TLR9,MyD88,NF-kB,IL-1βand TNF-αwere detected by PCR,and the protein expression levels of TLR9,MyD88 and NF-kB were determined by Western blot.Results Compared with the normal group,the body weight of the UC mice in the model group significantly decreased,with increased disease activity index(DAI)and shortened colon length.In addition,MPO,CP,IL-6,IL-1βand TNF-αof inflammatory factors in UC mice were increased significantly;the mRNA levels of miR-155,TLR9,MyD88,NF-kB,IL-1βand TNF-αwere significantly higher than those of normal mice,and the protein expression of TLR9,MyD88 and nF-kB was significantly increased.Conclusion miR-155 may participate in the UC inflammatory response by regulating the TLR9 signaling pathway,and the UC may be protected by inhibiting the miR-155-TLR9 signaling pathway,providing a potential target for the treatment.