环氧酶-2抑制剂对关节炎大鼠小肠黏膜的影响

Effect of cyclooxygenase-2 inhibitor on intestinal mucosa of arthritic rats

摘要:

目的 探讨环氧酶-2抑制剂对关节炎大鼠小肠黏膜的影响。方法 将32只雄性SD大鼠随机分为空白对照组、造模对照组、空白给药组和造模给药组，造模对照组、造模给药组给予弗氏完全佐剂右后足跖注射，空白对照组、空白给药组注射等量生理盐水。1周后造模给药组、空白给药组给予选择性环氧酶-2抑制剂塞来昔布（溶于1%甲基纤维素）灌胃28 d，空白对照组、造模对照组给予等量溶剂。处死大鼠后观察小肠黏膜大体损伤、病理评分，酶联免疫吸附试验检测末段小肠前列腺素浓度。结果 造模对照组与造模给药组模型复制第7天的足周径比较，差异无统计学意义（P >0.05），但两组分别与空白对照组和空白给药组比较，差异有统计学意义（P <0.05），空白对照组与空白给药组比较，差异无统计学意义（P >0.05）。空白对照组与造模对照组小肠黏膜损伤面积比较，差异有统计学意义（P <0.05），空白给药组与空白对照组比较，差异有统计学意义（P <0.05）。造模对照组、空白给药组和造模给药组组间小肠黏膜病理评分比较，差异无统计学意义（P >0.05），且空白对照组与其他3组比较，差异有统计学意义（P <0.05）。造模对照组、造模给药组小肠前列腺素浓度较空白对照组降低（P <0.05），造模对照组较空白给药组降低（P <0.05）。结论 塞来昔布可致大鼠小肠黏膜损伤；佐剂性关节炎大鼠存在小肠黏膜损伤，塞来昔布可增加其小肠黏膜损伤面积，但不增加损伤程度；塞来昔布对关节炎大鼠与正常大鼠的小肠黏膜损伤相似；小肠黏膜前列腺素浓度下降可能与全身炎症所致小肠损伤有关，但可能不是COX-2抑制剂小肠损伤的主要或起始事件。

Abstract:

Objective To establish rat models of adjuvant arthritis and to investigate the effects of selective cyclooxygenase-2 (COX-2) inhibitors on small intestinal mucosa.Methods Thirty-two rats were randomly divided into the blank control group, model control group, blank administration group and model administration group. The model control group and model administration group were injected with Freund's complete adjuvant at the right rear footpad, and the blank control group and blank administration group were given the same amount of normal saline. After 1 week, the blank administration group and model administration group were given celecoxib, a selective COX-2 inhibitor, dissolved in 1% methyl cellulose by gavage for 28 days, and the blank control group and model control group were given the same volume of solvents. The gross mucosal injury and pathological scores of small intestinal mucosa were observed after the rats were sacrificed. The level of prostaglandin in the end segment of small intestine was detected by ELISA.Results There was no difference in the foot perimeter at the 7th day of modeling between the model control group and the model administration group (P > 0.05), but the foot perimeter at the 7th day of modeling was different between the former two groups and the blank control group and the blank administration group, respectively (P < 0.05). However, no difference was found between the blank control group and the blank administration group (P < 0.05). The area of small intestinal mucosal injury was different between the blank control group and the model control group, and also between the blank administration group and the blank control group (P < 0.05). The pathological scores of small intestinal mucosa were not different among the model control group, blank administration group and the model administration group (P > 0.05), yet those in the former three groups were different from those in the blank control group (P < 0.05). The level of intestinal prostaglandin in the model control group and model administration group was lower than that in the blank control group (P < 0.05), and that in the model control group was lower compared with the blank administration group (P < 0.05).Conclusions Celecoxib causes intestinal mucosal injury in rats. The small intestinal injury is present in rats with adjuvant arthritis, and celecoxib may increase the area of small intestinal mucosal injury while not aggravating the degree of injury. The injury induced by celecoxib is comparable between the arthritis and normal rats. The reduction in the level of prostaglandin is potentially associated with the small intestinal mucosal injury caused by systemic inflammation but may not be the primary or initiating event of intestinal injury caused by COX-2 inhibitor.