姜黄素对肠黏膜损伤保护作用的实验研究

Protective effect of curcumin against methotrexate-induced small intestinal damage in rats

目的检测大鼠小肠炎模型肠黏膜通透性的改变,探讨姜黄素对大鼠小肠炎模型肠黏膜通透性的作用。方法应用氨甲碟呤制备大鼠小肠炎模型,实验设正常对照组、模型对照组、柳氮磺吡啶组(SASP,100mg/kg)、姜黄素组(Cur,100mg/kg),每天灌胃给药1次,共5天,第3天、第5天分别观察大鼠疾病活动指数(DAI)和肠黏膜损伤指数(CMDI),免疫组化法检测大鼠肠黏膜ICAM-1蛋白的表达。分光光度法检测血浆D-乳酸和小肠组织DAO水平。生化法检测大鼠小肠组织髓过氧化酶(MPO)活性。结果与正常组相比,小肠炎模型组DAI、CMDI、HS评分,D-乳酸和DAO水平及MPO活性明显升高(P<0.01)。ICAM-1表达明显增强(P<0.01)。姜黄素组DAI,CMDI,HS评分及D-乳酸、DAO、MPO活性较同期模型组有明显下降(P<0.01),ICAM-1表达也有不同程度降低(P<0.01)。结论大鼠小肠炎模型中肠黏膜通透性增高,肠黏膜受损。姜黄素可以改善肠黏膜的通透性,对大鼠小肠炎具有保护作用。

Objective To observe the changes in intestinal mucosal permeability in rats with methotrexate （MTX）-induced small intestinal damage and investigate the protective effects of curcumin. Methods The experiment was carried out using 4 groups of rats, namely the normal control group, enteritis model group, sulfasalazine （SASP） group and curcumin group. With the exception of the rats in the normal control group, all rats were subjected to intraperitoneal MTX injection to induce enteritis and received subsequent daily intragastric administration of SASP （100 mg/kg）, curcumin （100 mg/kg）, or normal saline for 5 days. The disease activity index （DAI）, colonic mucosal damage index （CMDI） and histological score （HS） of the rats were evaluated. The levels of diamine oxidase （DAO） and D-lactate were assessed using spectrophotometric assay, and myeloperoxidase （MPO） activity and intracellular adhesion molecule-1 （ICAM-1） protein expression were measured by biochemical and immunohistochemical methods, respectively. Results Compared with the normal control group, the rats in the model group showed significantly increased DAI, CMDI and HS and levels of DAO, D-lactate, ICAM-1 and MPO. Curcumin treatment resulted in significantly decreased DAI, CMDI, HS and lowered activities of D-lactate, ICAM-1 and MPO in comparison with the model group （P〈0.01）. Conclusion MTX induces increased mucosal permeability of the small intestines in rats, and curcumin may offer protective effects against MTX-induced rat enteritis by lowering the intestinal mucosal permeability.