Zhang Ling, Lv Yu min, Ye Si mao, Dong Xiu yun
Department of Gastroenterology, Peking University Third Hospital, Beijing 100083, China.
Beijing Da Xue Xue Bao Yi Xue Ban. 2008 Apr;40(2):195-9.
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).
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.
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 x 10(-2)+/-9.5 x 10(-3)) as compared with Group 2 (11.4 x 10(-2)+/-3.8 x 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.
Selective COX-2 inhibitor-celecoxib could decrease the expression of COX-2 in intestinal tissue, attenuate the inflammatory index of colon tissues of experimental colitis induced by TNBS. But the application of celecoxib resulted in exacerbation of colonic damage. These adverse events are probably relevant to the suppression of COX-2 expression in the neural cells of the myenteric plexus, leading to decrease of intestinal contractivity and peristalsis, enteroparalysis, megacolon and death of the rat.
评估塞来昔布（一种选择性COX - 2抑制剂）对三硝基苯磺酸（TNBS）诱导的大鼠结肠炎模型中结肠损伤加重的机制。
将大鼠随机分为四组。第1组和第2组为研究组。第3组和第4组为对照组。研究组通过在50%乙醇（0.25 mL）载体中结肠内给予TNBS（25 g/L）诱导结肠炎。研究组大鼠在结肠炎诱导前3小时开始口服给药，此后每天两次，持续7天，分别给予塞来昔布（1.25 mg/kg，第1组）和蒸馏水（1 mL/0.3 kg，第2组）。在对照实验中，第4组大鼠每天口服塞来昔布（1.25 mg/kg）两次，持续7天。第3组大鼠为健康对照大鼠。所有存活至实验结束（第7天）的大鼠均被处死，并评估结肠炎症的严重程度。通过免疫组织化学检测结肠组织中COX - 2蛋白表达。
与第2组相比，第1组的结肠损伤加重。第1组结肠组织的炎症指数（8.5±2.5）与第2组（13.5±1.9，P<0.05）相比显著降低。与第2组（11.4×10⁻²±3.8×10⁻²，P<0.05）相比，第1组COX - 2蛋白表达水平显著降低（3.7×10⁻²±9.5×10⁻³）。第1组肌间神经丛神经细胞中COX - 2表达的阳性率（30%）与第2组（90%，P<0.05）相比降低。第3组和第4组在结肠炎症指数、COX - 2蛋白表达水平以及肌间神经丛神经细胞中COX - 2表达阳性率方面未发现差异。
选择性COX - 2抑制剂塞来昔布可降低肠道组织中COX - 2的表达，减轻TNBS诱导的实验性结肠炎结肠组织的炎症指数。但塞来昔布的应用导致结肠损伤加重。这些不良事件可能与肌间神经丛神经细胞中COX - 2表达的抑制有关，导致肠道收缩性和蠕动降低、肠麻痹、巨结肠以及大鼠死亡。
