选择性COX-2抑制剂对实验性大鼠胃溃疡愈合及胃酸分泌的影响

Selective COX-2 inhibitor delays experimental gastric ulcer healing by stimulating gastric acid secretion in rats

目的明确选择性环氧合酶-2(COX-2)抑制剂对实验性大鼠胃溃疡愈合的影响,并从胃酸分泌的角度探讨其延缓胃溃疡愈合的机制。方法以乙酸性大鼠胃溃疡模型为基础,观察选择性COX-2抑制剂塞来昔布对胃溃疡愈合的影响及其对胃液总酸度、H+,K+-ATP酶mRNA和蛋白表达及壁细胞形态的影响。结果制模术后第9日,生理盐水组和塞来昔布组的溃疡面积(mm2)分别为11.9±3.1和19.7±3.8(P<0.01);制模术后第6日和第9日,塞来昔布组胃液总酸度和H+,K+-ATP酶mRNA和蛋白表达水平均显著高于生理盐水组,而两组壁细胞的分泌小管和微绒毛数量则均无明显差异。结论选择性COX-2抑制剂能显著延缓实验性大鼠胃溃疡的愈合过程,其延缓胃溃疡愈合的机制之一可能是通过刺激壁细胞胃酸分泌,加强了对溃疡底部新生肉芽组织的消化作用。

Objective To observe the effect of selective cyclooxygenase-2 （COX-2） inhibitor on the healing of experimental gastric ulcer in rats and explore its mechanisms in light of gastric acid secretion. Methods Gastric ulcers were induced in rats by an application of acetic acid to the serosal surface of the anterior gastric body. The effects of selective COX-2 inhibitor, celecoxib, on the healing of gastric ulcer, the total acidity of gastric juice, the expressions of H^＋, K^＋-ATPase mRNA and protein, and the ultrastructure of the parietal cell were observed in comparison with the effects of normal saline. Results Nine days after ulcer induction, the ulcer area was 11.9±3.1 mm^2 and 19.7±3.8 mm^2 in rats with normal saline and celecoxib treatments, respectively （P〈0.01 ）. The total acidity of gastric juice and the expressions of H^＋, K^＋-ATPase mRNA and protein in celecoxib group were significantly higher than that in normal saline group at both 6 and 9 days after ulcer induction, but no significant difference was found between the two groups in the amount of secretary canaliculus and microvillus, Conclusion Selective COX-2 inhibitor can significantly delay the healing of experimental gastric ulcer in rats, the mechanism of which might be associated with enhanced digestive action of gatric acid on the new granulation tissue at the ulcer base as a result of celecoxib-stimulated gastric acid secretion of the parietal cells.