姜黄素对肠炎大鼠肠黏膜基质金属蛋白酶-9的调控

Curcumin controls matrix metalloproteinase expression in colonic mucosa of rats with trinitrobenzene sulfonic acid-induced colitis

目的:探索姜黄素对炎症性肠病(IBD)模型大鼠肠黏膜炎症靶点基质金属蛋白酶(MMP)-9的影响.方法:建立以三硝基苯磺酸诱导的大鼠IBD模型.模型大鼠给予含20g/L姜黄素的饲料喂养,药物对照组给予含2g/LN乙酰半胱氨酸和5g/L柳氮磺胺吡啶的饲料喂养,模型组及正常对照组给予普通饲料喂养.评价肠炎大鼠死亡率及肠黏膜病理组织学评分.电泳迁移率改变分析法检测肠黏膜胞核NFκB活性的变化.应用Western印迹分析法检测肠黏膜细胞质IκB.半定量RTPCR检测MMP9mRNA的表达.结果:姜黄素可降低IBD模型大鼠死亡率及改善肠黏膜病理组织学症状.姜黄素可抑制IBD模型大鼠肠黏膜胞质IκB的降解并抑制胞核NF-κB的激活,同时降低MMP-9的表达.结论:姜黄素可预防和改善IBD鼠科模型中的实验性肠炎,调控MMP9的表达;MMP9可作为观察抗肠炎药物药效的指标之一,姜黄素对治疗IBD有应用前景.

AIM: To ascertain effects of NF-κB inhibitor curcumin on matrix metalloproteinase (MMP)-9 expression in the colonic mucosa of rats with trinitrobenzene sulfonic acid (TNBS)-induced colitis so as to screen out an anti-inflammatory target of curcumin. METHODS: Rats with TNBS-induced colitis were given a diet with 20 g/L curcumin. The medicine control rats were given a diet with 2 g/L N-acetylcysteine (NAC) and 5 g/L sulfasalazine (SASP) and the normal control rats and model rats were fed with regular diet. The changes in colonic mucosal histological scores and mortality were evaluated and the cell nuclear NF-κB activity in the colonic mucosa was evaluated by electrophoretic mobility shift assay. The cytoplasmic IκB protein in colonic mucosa was detected by Western Blot analysis and the MMP-9 messenger expressions in colonic tissue were assessed by semiquantitative reverse-transcription polymerase chain reaction. RESULTS: Degradations of cytoplasmic IκB protein in colonic mucosa were blocked by curcumin treatment. NF-κB activation in colonic mucosa was suppressed and the MMP-9 expression in colonic mucosa reduced in the curcumin-treated groups. Treatment with curcumin ameliorated the mortality and histopathologic signs of rats with TNBS-induced intestinal inflammation. CONCLUSIONS: NF-kappaB inhibitor, curcumin, can prevent and ameliorate experimental colitis in rats. MMP-9 expression can be controlled by curcumin. MMP-9 can be a medicine target for inflammatory bowel diseases.