Arisawa Tomiyasu, Harata Masao, Kamiya Yoshio, Shibata Tomoyuki, Nagasaka Mitsuo, Nakamura Masakatsu, Fujita Hiroshi, Hasegawa Shin, Nakamura Masahiko, Mizuno Tamaki, Tahara Tomomitsu, Ohta Yoshiji, Nakano Hiroshi
Department of Gastroenterology, Fujita Health University, School of Medicine, Toyoake, Japan.
Digestion. 2006;73(1):32-9. doi: 10.1159/000092012. Epub 2006 Mar 14.
Proton pump inhibitors (PPI) and prostaglandin (PG) preparations are believed to both prevent NSAID-induced gastric ulcers and promote the delayed healing of gastric ulcers by NSAIDs, but it remains unclear which of these drugs is superior. The aim of this study was to clarify which achieved better healing of NSAID-induced gastric ulcers, not only with respect to epithelialization but also repair of the submucosal tissues.
We used acetic acid to induce gastric ulcers in rats, and compared the changes between a control group, NSAID group, NSAID + PPI group and NSAID + PG group. After removing the stomach of each animal, an ulcer index was calculated and the collagen content and type III collagen content of granulation tissue were measured. We also studied fibroblast dynamics, including proliferation, collagen synthesis, differentiation into myofibroblasts, and apoptosis.
Indomethacin prevented re-epithelialization of the ulcers, interfered with fibroblast function, and also delayed the replacement of type III collagen. Omeprazole promoted epithelialization, but could not fully reverse the influence of indomethacin on granulation tissue maturation. A concomitant dose with misoprostolreversed it completely.
From our point of view in this study in the use of experimental ulcers, it was thought that compensation of PG should have priority to gastric acid inhibition in terms of healing of NSAID-induced gastric ulcer.
质子泵抑制剂(PPI)和前列腺素(PG)制剂被认为既能预防非甾体抗炎药(NSAID)引起的胃溃疡,又能促进NSAID所致胃溃疡的延迟愈合,但哪种药物更具优势尚不清楚。本研究的目的是明确哪种药物能使NSAID引起的胃溃疡愈合更好,不仅在表皮化方面,而且在黏膜下组织修复方面。
我们用乙酸诱导大鼠胃溃疡,并比较了对照组、NSAID组、NSAID + PPI组和NSAID + PG组之间的变化。在摘除每只动物的胃后,计算溃疡指数,并测量肉芽组织的胶原蛋白含量和III型胶原蛋白含量。我们还研究了成纤维细胞动力学,包括增殖、胶原蛋白合成、分化为肌成纤维细胞以及凋亡。
吲哚美辛阻止溃疡重新上皮化,干扰成纤维细胞功能,还延迟III型胶原蛋白的替代。奥美拉唑促进上皮化,但不能完全逆转吲哚美辛对肉芽组织成熟的影响。与米索前列醇同时给药可完全逆转这种影响。
从我们在本实验性溃疡研究中的观点来看,就NSAID引起的胃溃疡愈合而言,认为在PG补偿方面应优先于胃酸抑制。