塞来昔布使实验性结肠炎损伤加重的作用机制  

Mechanism of exacerbation of colonic damage in experimental colitis treated with celecoxib

作　　者：张玲[1] 吕愈敏[1] 叶思懋[1] 董秀云[1] 

机构地区：[1]北京大学第三医院消化科,北京100083

出　　处：《北京大学学报（医学版）》2008年第2期195-199,共5页Journal of Peking University:Health Sciences

摘　　要：目的:探讨选择性环氧合酶(COX)-2抑制剂塞来昔布使2,4,6-三硝基苯磺酸(TNBS)诱导的大鼠结肠炎损伤加重的作用机制。方法:将大鼠随机分为4组:第1组和第2组为造模组,第3组和第4组为对照组。用0.25mLTNBS乙醇溶液[含质量浓度为25g/L的TNBS,50%(体积分数)乙醇]灌肠,诱导大鼠慢性实验性结肠炎模型。在造模前3h,造模组第1组大鼠以塞来昔布(1.25mg/kg)灌胃,第2组以蒸馏水(1mL/0.3kg)灌胃,此后一天两次灌胃,直到第7天;对照组不造模,其中第4组以塞来昔布(1.25mg/kg)灌胃,一天两次,直到第7天;第3组大鼠为正常对照组。于第7天实验结束时处死所有存活动物,观察病变处肠组织的炎症程度,同时用免疫组化方法检测肠组织中COX-2的表达。结果:造模组大鼠中,第1组的结肠扩张程度、溃疡面积、肠壁厚度均大于第2组。第1组的结肠炎炎症指数为8.5±2.5,显著低于第2组13.5±1.9(P<0.05)。第1组的结肠组织COX-2的面密度为3.7×10-2±9.5×10-3,显著低于第2组(11.4×10-2±3.8×10-2,P<0.05)。第1组的结肠肠肌间神经丛COX-2表达的阳性率为30%,显著低于第2组(90%,P<0.05)。第3组与第4组比较,炎症指数、结肠组织COX-2面密度、结肠肠肌间神经丛COX-2表达阳性率差异均无统计学意义。结论:选择性COX-2抑制剂塞来昔布使TNBS肠炎大鼠结肠病变处组织学炎症程度减轻,COX-2表达减少,但损伤加重。其机制可能与塞来昔布对大鼠肠肌间神经丛COX-2产生抑制,与肠道收缩力减弱、蠕动减少,与肠麻痹、巨结肠的形成有关。Objective： To assess the mechanism of exacerbation of colonic damage in rat colitis model induced by trinitrobenzene sulfonic acid （TNBS） treated with celecoxib （a selective COX-2 inhibitor）. Methods： The rats were randomized into four groups. Group 1 and Group 2 were study groups. Group 3 and Group 4 were control groups. Colitis was induced by intracolonic administration of TNBS （25 g/L） in a vehicle of 50% ethanol （0.25 mL） of study groups. The rats of study groups were treated orally, beginning 3 h before induction of colitis and continuing twice per day thereafter for up to 7 d, with celecoxib （ 1.25 mg/kg, Group 1 ） and distilled water （ 1 mL/0.3 kg, Group 2） respectively. In control experiments, the rats of Group 4 were treated orally with celecoxib （ 1.25 mg/kg） twice per day for up to 7 d. Group 3 rats were healthy control rats. All the rats that survived until the end of the experiment （ d 7 ） were killed and the severity of colonic inflammation was assessed. The COX-2 protein expression in colon tissues was examined by immunohistochemistry. Results： The colonic damage of Group 1 was exacerbated as compared with Group 2. The inflammatory index of colon tissues of Group 1 （8.5 ± 2.5 ） was significantly reduced, as compared with Group 2 （ 13.5 ± 1.9, P 〈0.05 ）. The levels of COX-2 protein expression was decreased significantly in Group 1 （ 3.7 × 10^-2 ±9.5 × 10^-3 ） as compared with Group 2 （ 11.4 × 10^ -2 ± 3.8 × 10^-2, P 〈 0.05）. The positive rate of COX-2 expression in neural cells of the myenteric plexus in Group 1 （ 30% ） was decreased, as compared with Group 2 （ 90%, P 〈 0.05 ）. No difference was found in the inflammatory index, the levels of COX-2 protein expression and the positive rate of COX-2 expression in neural cells of the myenteric plexus of Group 3 and Group 4. Conclusion： Selective COX-2 inhibitor-celecoxib could decrease the expression of COX-2 in intestinal tissue, attenuate the inflammatory index of colon tiss

关 键 词：结肠炎 疾病模型 动物 环加氧酶抑制药 

分 类 号：R574.62[医药卫生—消化系统]