奥扎格雷钠对TNBS诱导的结肠炎大鼠的治疗作用  

Therapeutic Effects of Ozagrel Sodium on TNBS-induced Colitis in Rats

作　　者：杨英[1] 孙静[1] 陈隆典[2] 

机构地区：[1]苏州大学附属常州市第一人民医院消化科,213003 [2]南京大学医学院附属鼓楼医院消化科

出　　处：《胃肠病学》2010年第12期745-748,共4页Chinese Journal of Gastroenterology

摘　　要：背景：近期研究证实血小板活化在炎症性肠病（IBD）的发病中起重要作用.目的：探讨血栓烷合成酶抑制剂奥扎格雷钠对三硝基苯磺酸（TNBS）诱导的大鼠结肠炎模型的治疗作用.方法：21只Sprague-Dawley（SD）鼠随机分为结肠炎模型组、地塞米松治疗组、奥扎格雷钠治疗组,每组7只;另取4只大鼠作为正常对照组.TNBS建模后第2～6d分别给予地塞米松、奥扎格雷钠和0.9%NaCl溶液皮下注射,于第7 d处死所有大鼠.检测大鼠体质量改变、结肠重量长度比、结肠大体和病理评分,以放射免疫法检测血浆P-选择素（CD62P）、血栓烷B2（TXB2）和6-酮-前列腺素F（6-k-PGF）1α,化学比色法测定结肠组织髓过氧化物酶（MPO）、丙二醛（MDA）、诱生型一氧化氮合酶（iNOS）.结果：地塞米松治疗组和奥扎格雷钠治疗组的肠道病理损伤较结肠炎模型组明显减轻,血浆CD62P、TXB2、TXB2/6-k-PGF1α和结肠组织MPO、MDA、iNOS明显降低（P＜0.05）,血浆6-k-PGF1α水平明显增高（P＜0.05）.结论：奥扎格雷钠可通过抑制血小板活化明显减轻TNBS结肠炎大鼠的肠道炎症损伤,提示抗血小板治疗有望成为IBD新的治疗方法.Background： Recent studies suggest that platelet activation plays an important role in the pathogenesis of inflammatory bowel disease （IBD）. Aims： To investigate the therapeutic effects of ozagrel sodium, an inhibitor of thromboxane synthase, on trinitrobenzene sulfonic acid （TNBS）-induced colitis in rats. Methods： Twenty-one Sprague- Dawley （SD） rats were randomized into colitis group, dexamethasone treatment group and ozagrel sodium treatment group, with seven rats in each group, and another 4 rats were served as normal controls. Dexamethasone, ozagrel sodium and normal saline solution were injected subcutaneously, respectively, on day 2-6 after the establishment of colitis. On day 7, all animals were sacrificed. The change of body weight, weight-to-length ratio of colon, and macroscopic and pathologic score of colon were assessed. Plasma P-selectin （CD62P）, thromboxane B2 （TXB2） and 6-keto-prostaglandin F （6-k-PGF） 1α levels were determined by radioirnmunoassay, and colon myeloperoxidase （MPO）, malondialdehyde （MDA） and inducible nitric oxide synthase （iNOS） were determined by chemical colorimetric analysis. Results： Colonic pathologic score, plasma CD62P, TXB2 and TXBJ6-k-PGF1α, colon MPO, MDA and iNOS of dexamethasone treatment group and ozagrel sodium treatment group were significantly lower than those of colitis group （P〈0.05）, while plasma 6-k-PGF1α much higher than that of colitis group （P〈0.05）. Conclusions： Ozagrel sodium ameliorates the TNBS-induced colonic mucosal inflammation through inhibiting activation of platelet in rats, which suggests that anti-platelet therapy might be a potential therapeutic strategy for IBD.

关 键 词：奥扎格雷钠 三硝基苯磺酸 结肠炎 P选择素 血栓烷B2 过氧化物酶 丙二醛 一氧化氮合酶 

分 类 号：R574.62[医药卫生—消化系统]