实验性结肠炎p38丝裂原活化蛋白激酶表达的研究

The study on expression of p38 mitogen-activated protein kinases in experimental colitis

目的观察三硝基苯磺酸(TNBS)诱导的大鼠结肠炎结肠组织p38MAPK表达与激活及大鼠血清TNF-α、IL-10水平变化,探讨p38MAPK在实验性结肠炎中的作用与机制。方法20只SD大鼠随机分为正常对照组(N)与模型组(M),TNBS/乙醇法构建结肠炎模型,观察炎症活动指数(DAI)、大体形态损伤指数(CMDI)、组织学损伤指数(TDI),ELISA法检测血清TNF-α、IL-10水平,免疫组化染色检测大鼠结肠p38MAPK、p-p38MAPK表达。结果与N组相比,M组DAI、CMDI、TDI显著升高(P<0.01),血清TNF-α升高,IL-10水平下降(P<0.01),结肠组织p38MAPK表达增加(P<0.05),p-p38MAPK表达显著增加(P<0.01)。结论p38MAPK在实验性结肠炎的表达与激活均有明显增加,可能通过调节TNF-α、IL-10等细胞因子的表达参与结肠炎的发病。

Objective To study the expression and activation of p38MAPK and the changes of TNF-α, IL-10 in TN- BS-induced colitis, and to explore the effect and mechanism of p38MAPK in experimental colitis. Methods Twenty male SD rats were randomly divided into normal control group （N） and model group （M）. Colitis was induced by intrarectal administration of TNBS/ethanol. The colonic inflammation including disease activity index （DAI）, colonic macroscopic damage index （CMDI） and tissue damage index （TDI） were observed, the levels of IL-10, TNF-α in serum were detected by ELISA, and the expressions of p38MAPK, p-p38MAPK in the colon tissues of rats were detected by immunohistochemical method. Results Compared with normal control group, the DAI, CMDI and TDI were increased significantly （P 〈 0.01 ） in model group, the level of TNF-α in serum increased （P 〈0.01 ）, and the level of IL-10 reduced （P 〈 0.01 ）. The expressions of p38MAPK increased （P 〈 0.05） in colonic tissues and p-p38MAPK increased significantly （P 〈0.01 ）. Conclusion The expression and activation of p38MAPK increased significantly in experimental colitis, and it may play a key role in pathogenesis of experimental colitis through regulating expressions of TNF-α, IL-10.