罗格列酮对大鼠溃疡性结肠炎的疗效及其机制

Effect of Rosiglitazone on Rat Ulcerative Colitis and Probable Mechanism

目的观察罗格列酮对大鼠溃疡性结肠炎的疗效并探讨其可能存在的机制。方法应用三硝基苯磺酸(TNB)/乙醇灌肠制备大鼠溃疡性结肠炎模型。实验设正常对照组、模型对照组、阳性药物组(柳氮磺胺吡啶组,100 mg/kg)、罗格列酮给药组(2 mg、4mg、8 mg/kg),每天灌胃给药1次,给药时间从造模后第2天开始至实验结束共8 d,观察大鼠疾病活动指数(DAI)、结肠黏膜损伤指数(CMDI)及组织学评分(HS)。生化法检测大鼠结肠组织髓过氧化物酶(MPO)、超氧化物歧化酶(SOD)活性及丙二醛(MDA)的含量。结果与正常组相比,模型组大鼠DAI、CMDI、HS明显增加(P<0.01),结肠组织MPO活性、MDA水平显著升高(P<0.01),SOD活性下降(P<0.01)。罗格列酮4 mg、8 mg/kg和SASP可不同程度改善DAI、CMDI和HS(P<0.05,P<0.01),降低MPO活性和MDA水平(P<0.01),增加SOD活性(P<0.01)。结论罗格列酮对大鼠溃疡性结肠炎有保护作用,其机制可能与减少脂质氧化,增加清除氧自由基的能力有关。

Objective To investigate the effect of rosiglitazone on rat colitis and mechanism. Methods Rat colitis model was induced by 2,4,6-trinitrobenzene sulfonic acid（TNB） with ethanol. The experimental animals were randomly divided into 6 greups ： normal group, model group, SASP group （ 100 mg/kg）, rosiglitazone group （2 mg ,4 mg ,8 mg/kg）. The saline, SASP, rosiglitazone were administered by garage resepectively, 1 time per day,from 24 h after the establishment of model to the end of experiment,added up to 8 days. The disease activity index（DAI） ,colon mucosa damage index（CMDI） and histological score（HS） of the rats were observed and evaluated. The level of myeloperoxidase（MPO） and malondia-dehyde（MDA） along with superexide dismutase（SOD） activity were measured by biochemical methods. Results Compared with normal greup, the DAI , CMDI and HS in model group increased significantly, the level of MPO and M DA were augmented, however the SOD activity reduced remarkably. Rosiglitazone can ameliorate DAI,CMDI, HS, reduce the level of MPO and MDA, elevate the SOD activity. Conclusion Rosiglitazone has beneficial effect on rat ulcerative colitis. Reducing lipid perexidation and resisting oxygen free radical may the probable mechanism.