Fas/FasL、p38 MAPK通路在溃疡性结肠炎大鼠中的表达及雷公藤多苷的作用

目的探讨Fas/FasL及p38 MAPK信号通路在溃疡性结肠炎(UC)大鼠中的表达变化,以及雷公藤多苷(TWP)对其的影响。方法采用2,4,6-三硝基苯磺酸(TNBS)/乙醇灌肠法建立UC大鼠模型。对大鼠结肠炎症进行评分;以表达谱技术分析Fas/FasL的差异表达,并用real-time PCR技术进行验证;继而DAVID数据库信号通路分析显示,Fas/FasL调节UC的炎症活动涉及p38 MAPK信号通路,同时在表达谱中分析此信号通路中的相关分子,并以real-time PCR法加以验证;最后采用RT-PCR法及Western blot法检测该信号通路末端炎症因子的表达。结果 UC大鼠结肠炎症评分明显升高,TWP能明显降低其炎症评分; Fas/Fas L系统及p38 MAPK通路中的Fas L、MAPK14(p38α)、TNF-α、IL-1β在UC大鼠炎症活动时均呈上调表达,TWP能够明显下调上述指标的表达。结论 TWP能够通过Fas/Fas L系统及p38MAPK信号通路对UC炎症活动进行调控。

Effect of Tripteryginum wilfordii polyglycoside on Fas/FasL and p38 MAPK signaling pathway expression in ulcerative colitis rats

Aim To investigate the expression changes of Fas/FasL and its related signaling pathway p38 MAPK in ulcerative colitis(UC) rats and the effects of Tripterygium wilfordii polycoride(TWP). Methods TNBS and ethanol enema method were adopted to build the UC rat model, and colon inflammation in rats was assessed;the differential expression of Fas/FasL was analyzed by expression profiling method, and verified by real-time PCR. Subsequently, pathway analysis in DAVID database showed that Fas/FasL might involve p38 MAPK signaling pathway in regulating UC inflammatory activities, and the related molecules in this signaling pathway were analyzed by the expression profiling method and verified by real-time PCR. Finally, the expression of the terminal inflammatory factors of the pathway were detected by RT-PCR and Western blot. Results In UC rats, the gross morphological damage and histopathological injury scores significantly increased, which could be reduced by TWP. The trend of FasL was in consistent with that of MAPK14 (p38α), TNF-α and IL-1β in Fas/FasL system and the p38 MAPK signaling pathway, and the expression of them were up-regulated in inflammatory activity, which can be down-regulated by TWP. Conclusion TWP can regulate the inflammatory activity of UC through Fas/FasL system and the p38 MAPK signaling pathway.