Kakei N, Ichinose M, Tsukada S, Tatematsu M, Tezuka N, Furihata C, Yahagi N, Matsushima M, Miki K, Kurokawa K
First Department of Internal Medicine, Faculty of Medicine, University of Tokyo, Japan.
Biochem Biophys Res Commun. 1993 Nov 30;197(1):310-8. doi: 10.1006/bbrc.1993.2477.
The effects of omeprazole on developing rat stomach mucosa were investigated. Infant rats were given subcutaneous injections of either omeprazole (25 mg/kg body weight/day) or vehicle once a day from the day after birth. As a result, omeprazole caused an elevation of mucosal pH and suppressed an increase in mucosal pepsinogen and its mRNA levels during stomach development. Histologically, these changes were associated with a reduction in mature pepsinogen-producing cells throughout stomach mucosa. Omeprazole also caused a delay in the expression of cathepsin E in surface mucous cells and an increase in labeled cells with bromodeoxyuridine. Thus, the present results indicate that omeprazole induces an increase in mucosal cell proliferation and delays the differentiation of developing rat stomach mucosa. Since the observed changes were remarkable especially from days 15 to 21 after birth when significant development of acid secretion occurs, the effects of omeprazole appear to be related with the potent acid inhibitory effect of the reagent.
研究了奥美拉唑对发育中大鼠胃黏膜的影响。从出生后第二天起，给幼鼠每天皮下注射奥美拉唑（25毫克/千克体重/天）或赋形剂。结果，奥美拉唑导致黏膜pH值升高，并在胃发育过程中抑制了黏膜胃蛋白酶原及其mRNA水平的增加。组织学上，这些变化与整个胃黏膜中成熟胃蛋白酶原产生细胞的减少有关。奥美拉唑还导致表面黏液细胞中组织蛋白酶E的表达延迟以及溴脱氧尿苷标记细胞增加。因此，目前的结果表明，奥美拉唑可诱导黏膜细胞增殖增加，并延迟发育中大鼠胃黏膜的分化。由于观察到的变化在出生后15至21天尤为显著，此时胃酸分泌显著发育，奥美拉唑的作用似乎与其强大的酸抑制作用有关。
