p38丝裂原活化蛋白激酶特异性抑制剂SB203580对溃疡性结肠炎大鼠血清IL-6和IL-1β的影响

Effects of p38 mitogen-activated protein kinase inhibitor SB203580 on the levels of IL-1β and IL-6 in the serum of rats with TNBS-induced colitis

目的观察p38丝裂原活化蛋白激酶(MAPK)特异性抑制剂SB203580对溃疡性结肠炎大鼠血清IL-6和IL-1β的影响,探讨p38MAPK在溃疡性结肠炎中的可能作用。方法 45只健康SD大鼠随机均分为正常对照组、模型组、SB203580组。采用三硝基苯磺酸(TNBS)制备大鼠溃疡性结肠炎模型,免疫组织化学方法检测大鼠肠组织活化转录因子2(p-ATF2)表达,ELISA法检测大鼠血清白介素-6(IL-6)和白介素-1β(IL-1β)表达水平,并观察肠道大体形态和组织学改变;同时分析p-ATF2水平与IL-6及IL-1β含量的关系。结果与正常对照组相比,模型组大鼠肠组织p-ATF2水平、血清IL-6及IL-1β含量显著增高(P<0.05),SB203580组p-ATF2表达与血清IL-6、IL-1β水平均明显低于结肠炎模型组(P<0.05),p-ATF2水平与IL-6及IL-1β含量呈正相关(P<0.05)。结论 p38MAPK抑制剂SB203580通过下调p-ATF2活性及IL-6、IL-1β表达,对TNBS诱导的溃疡性结肠炎大鼠起保护作用。

Objective To investigate the effect of p38 mitogen-activated protein kinase inhibitor SB203580 on the serum levels of IL-1βand IL-6 in rats with TNBS-induced colitis,and to explore the role of p38 in the pathogenesis of colitis.Methods Forty-five healthy SD rats were randomly divided into three groups:normal group,model group,SB203580 group.The rat models of colitis were induced by 2,4,6-trinitrobenzene sulfonic acid(TNBS),the expression of p-ATF2 in colon tissue was examined by immunohistochemistry,the serum levels of IL-1βand IL-6 in rats were detected by ELISA.And the colonic mucosal damage index and histological score were evaluated.At the same time,the relationship between p-ATF2 and IL-1β,IL-6 was analysed.Results Compared with normal group,the expression of p-ATF2 and the serum levels of IL-1βand IL-6 were significantly increased in model group (P<0.05),and the above indicators in rats of SB203580 group was lower than that of model group(P<0.05).There was positive correlation between the expression of p-ATF2 and the levels of IL-1β,IL-6 respectively(r=0.980,0.988,P<0.05).Conclusion p38 MAPK inhibitor SB203580 has protective effects on TNBS-induced ul-cerative colitis through down-regulating the expression of p-ATF2 and levels of IL-1β,IL-6.