5-氨基水杨酸通过PPARγ在鼠结肠炎中发挥抗炎作用  

Anti-inflammatory effect of 5-aminosalicylic acid via peroxisome proliferation activated receptor gammar in rats colitis

作　　者：杨彩虹[1] 吴正祥[1] 吴强[2] 杨枫[2] 葛相栓[1] 姚霞[1] 

机构地区：[1]安徽医科大学附属省立医院消化内科,合肥230001 [2]安徽医科大学病理学教研室,合肥230032

出　　处：《安徽医科大学学报》2008年第4期422-425,461,共5页Acta Universitatis Medicinalis Anhui

摘　　要：目的探讨5-氨基水杨酸是否通过过氧化物酶体增殖物激活受体γ(PPARγ)途径在三硝基苯磺酸(TNBS)诱导的结肠炎模型大鼠中发挥抗炎作用。方法40只♂SD大鼠,随机分为5组,每组8只。设立空白对照组,另4组利用TNBS/乙醇制备大鼠结肠炎模型后,设模型组、GW9662组、柳氮磺吡啶(SASP)组、GW9662+SASP组。造模后第2天起每日灌胃、腹腔注射给药,连续2周。结肠炎症的评价包括炎症活动指数、结肠大体及组织学评分,血中白细胞介素(IL)2、IL-10水平,结肠PPARγ、NF-κBp65表达。结果与结肠炎模型组比,SASP组能明显降低DAI评分,改善结肠大体、组织病理学损伤,血IL-2降低,IL-10升高,结肠内PPARγ表达增加,NF-κBp65表达减少,差异有显著性(P<0.05),且模型组大鼠结肠黏膜PPARγ表达与NF-κBp65表达呈负相关;而GW9662+SASP组大鼠DAI、结肠大体、组织病理学损伤,较模型组及SASP组无改善,PPARγ表达增加(P<0.05),但NF-κBp65无明显变化。结论5-氨基水杨酸可能通过PPARγ途径,负性调节NF-κB的表达,从而减少促炎介质(IL-2)、增加抑炎介质(IL-10)的释放,在TNBS诱导的结肠炎模型大鼠中发挥抗炎作用。Objective To further study whether 5-aminosalicylic acid has anti-inflammatory effects by peroxisome proliferation activated receptor gammar （PPARγ） in rats with trinitro-benzene-sulfonic acid （TNBS） induced colitis. Methods Forty male SD rats weighing 200 g ± 20 g were randomly divided into 5 groups （ n = 8 per group）, including one normal control group and 4 experiment groups. Colitis was induced by intra-rectal administration of TNBS/ethanol. The four experiment groups were model group, GW9662 group, SASP group and GW9662 ＋ SASP group respectively. The drug was administered intra-peritoneally and by gastric irrigation daily starting from 24 h after the establishment of colitis model to the end of the experiment. The rats were sacrificed after two weeks. The colonic inflammation including disease activity index（ DAI）, colonic macroscopic and histological score, levels of interleukin （IL）2, IL-10 were evaluated by Elisa. The expression of NF-κBp65, PPARγ was examined by immunohistochemistry. Results As compared with the model group, the DAI, colonic macroscopic and histological score, the levels of IL-2 in the blood and the expression of NF-κBp65 in the colon tissues of the rats in the SASP group were significantly decreased ; while the levels of IL-10 and the expression of PPARγ were significantly increased. The expression of NF-κBp65 and PPARγ in rat colon mucosa of colitis model was positively correlated, but these levels in the GW9662 ＋ SASP group were as similar as those observed in the colitis model group, except for the expression of PPARγ. Conclusion 5-ASA-mediated salutary effects on the rat colitis induced by TNBS appear to be mediated at least in part via PPARγ activation, which inhibits the activation of NF-κB, down-regulates the expression of IL-2 and increasing-regulates the expression of IL-10.

关 键 词：PPARΓ 氨基水杨酸类/治疗应用 结肠炎/药物疗法 疾病模型 动物 

分 类 号：R574.620.53[医药卫生—消化系统] R978.34[医药卫生—内科学]