选择性环氧合酶-2抑制剂塞来昔布在实验性结肠炎中的作用机制

Effects and mechanism of celecoxib on rat colitis induced by trinitrobenzene sulfonic acid

目的 明确选择性环氧合酶 (COX) 2抑制剂—塞来昔布对 2 ,4 ,6 三硝基苯磺酸 (TNBS)诱导的大鼠结肠炎的作用 ,并初步探讨其作用机制。方法 将大鼠分为四组 :第 1组和第 2组为造模组 ,第 3组和第 4组为对照组。用 0 .2 5mlTNBS乙醇溶液 (TNBS浓度 2 5mg/ml,乙醇浓度 5 0 % )灌肠 ,诱导大鼠慢性实验性结肠炎模型。造模组大鼠于造模前 3h开始 ,分别给予塞来昔布 (1.2 5mg/kg ,第 1组 )和蒸馏水 (第 2组 ) ,每天 2次 ,共 7d。第 3组大鼠为正常对照组。第 4组大鼠以塞来昔布 (1.2 5mg/kg)灌胃 ,每天 2次 ,共 7d。于第 7天实验结束时处死所有存活动物 ,观察结肠黏膜的损伤程度 ,同时用放射免疫分析法测定结肠黏膜前列腺素E2 (PGE2 )水平。结果 造模组大鼠结肠损伤积分分别为11.15± 3.30 (第 1组 )和 8.5 0± 2 .82 (第 2组 ) ,均显著高于正常对照组 0 .6 2± 0 .0 9(P值均 <0 .0 1)。第 1组的结肠损伤积分显著高于第 2组 (P <0 .0 5 )。第 3组和第 4组的积分差异无显著性。造模组大鼠结肠黏膜PGE2浓度分别为 (12 .0 0± 4 .33)pg/ μg(第 1组 )和 (17.2 0± 9.6 2 ) pg/ μg(第 2组 ) ,均显著高于正常对照组的 (6 .0 2± 3.39) pg/ μg ,(P值均 <0 .0 5 )。第 1组的PGE2浓度显著低于第 2组 (P <0 .0 5 )

Objective An investigation was conducted to assess the effects and mechanism of celecoxib [a selective cyclooxygenase(COX) 2 inhibitor] on a rat colitis model induced by trinitrobenzene sulfonic acid (TNBS). Methods The rats were divided into four groups. Group 1 and group 2 were experimental groups. Group 3 and group 4 were control groups. Colitis was induced by intracolonic administration of TNBS (25 mg/ml) in a vehicle of 50% ethanol (0.25 ml) in rats of experiment groups. Three hours before induction of colitis ,the rats were beginning and continuing to treat orally with celecoxib (1.25 mg/kg, group 1) and distilled water (1 ml/0.3 kg, group 2) twice per day for 7 days , respectively. The rats in group 4 were treated orally with celecoxib (1.25 mg/kg) twice per day for 7 days. Group 3 served as healthy control. All rats that survived until the end of the experiment (7 d) were killed and the severity of damage were assessed. The prostaglandin E2 (PGE2) concentrations of colonic mucosa were tested by radioimmunoassay. Results The colonic damage scores were 11.15±3.3 in group 1 and 8.50±2.82 in group 2. Both were significantly higher than that of group 3 (0.62±0.09)( P <0.01). The colonic damage score of the group 1 was significantly higher than that of group 2 ( P <0.05). No difference was found in scores between group 3 and group 4. The PGE2 concentrations were(12.00±4.33)pg/μg in group 1 and (17.20± 9.62 ) pg/μg in group 2. Both were significantly higher than that of group 3 [ (6.02±3.39 )pg/μg, P <0.05]. The PGE2 concentration of the group1 was decreased significantly compared with that in group 2 ( P <0.05). No difference was found in PGE2 concentration between group 3 and group 4. Conclusions These results suggest that treatment with celecoxib (selective COX 2 inhibitor) resulted in exacerbation of inflammation associated colonic injury in experimental colitis induced by TNBS. The preliminary study shows that the mechanism is related to the suppression caused by COX 2 inhibitor for the PGs derived from COX 2, but further study is still needed for identifying if there are some other related reasons.