归巢受体与TLR4在溃疡性结肠炎小鼠肠道中的相关性研究

Research of correlation between homing receptors and TLR4 in intestines of mice with ulcerative colitis

目的比较溃疡性结肠炎模型小鼠结肠组织中淋巴细胞归巢受体CCR2、CCR9与Toll样受体4(TLR4)随时间的变化及其相关性,以探讨TLR4介导归巢受体引起的结肠炎症在溃疡性结肠炎中的可能作用机制。方法 50只BALB/c小鼠随机分为5组,分别用于DSS造模的第0天、第3天、第6天、第9天、第12天取得各组小鼠的结肠标本,用RT-PCR和Western blotting的方法半定量检测CCR2、CCR9、TLR4在基因和蛋白水平上的表达。结果①正常小鼠结肠内无TLR4表达,CCR2、CCR9的表达均呈低水平。②随着造模时间的延长,UC模型小鼠结肠内TLR4、CCR9、黏膜炎症评分均呈进行性升高,CCR2则维持在较低水平。③各组小鼠TLR4与CCR9的表达呈正相关,TLR4与CCR2无相关。结论 TLR4介导的淋巴细胞归巢可能参与了溃疡性结肠炎的致病机制,其信号传导依赖于CCR9而不是CCR2。

【Objectives】 To observe the changes of lymphocyte homing receptors CCR2,CCR9 and Toll-like receptor 4（TLR4） and their correlations in colon tissue of ulcerative colitis mice with time.To explore the possible mechanism of colitis induced by TLR4 mediated lymphocyte homing receptor in ulcerative colitis.【Methods】 50 BALB/c mice were randomly divided into 5 groups,specimens of colon tissue of each group mice were respectively obtained at day 0,days 3,days 6,days 9,days 12 of feeding DSS,RT-PCR and Western blotting method were used to semi-quantitative detect expression of CCR2,CCR9 and TLR4.【Results】 There is no expression of TLR4 in colon of normal mice.Expression of CCR2,CCR9 were low in normal mice.Expression of TLR4,CCR9 and severity of pathology in colon increased steply with time after feeding DSS in mice,while CCR2 kept on low level.Expression of TLR4 and CCR9 in mice are positively correlated,and there is no correlation between TLR4 and CCR2.【Conclusions】 Lymphocyte homing mediated by TLR4 may be involved in the pathogenesis of ulcerative colitis,its signal transduction is dependent on CCR9 instead of CCR2.