Azuma T, Dojyo M, Ito S, Yamazaki Y, Miyaji H, Ito Y, Suto H, Kuriyama M, Kato T, Kohli Y
Second Department of Internal Medicine, Faculty of Medicine, Fukui Medical University, Japan.
Dig Dis Sci. 1999 Jun;44(6):1177-83. doi: 10.1023/a:1026684425642.
c-Kit is a receptor tyrosine kinase, and it is encoded by the mouse W locus. Mutant W/Wv mice develop spontaneous gastric antral ulcers. The aim of the present study was to investigate the pathogenesis of these gastric ulcers and to examine the effects of two antiulcer drugs; a proton pump inhibitor (2{[4-(3-methoxypropoxy)-3-methylpyridine-2-yl]methyl-sulfinyl}-1H -benzimidazole sodium salt, rabeprazole) and a mucosal protective drug (geranylgeranylacetone, GGA), on the gastric ulcers. The inhibition of the gastric acid secretion by rabeprazole (30 mg/kg body weight, subcutaneous injection once a day for six weeks) significantly increased the gastric ulcer formation compared to the controls. In contrast, the GGA treatment (100 mg/kg body weight, oral administration for six weeks) significantly inhibited the ulcer formation. Bile reflux was seen in these mutant mice, and they showed no cyclic intense contractions in the gastric antrum. These results suggest that bile reflux due to the disturbance of gastric antral movement is a cause of the spontaneous gastric ulcers in W/Wv mice.
c-Kit是一种受体酪氨酸激酶，由小鼠W位点编码。突变的W/Wv小鼠会自发发生胃窦溃疡。本研究的目的是探讨这些胃溃疡的发病机制，并研究两种抗溃疡药物的作用；一种质子泵抑制剂（2-{[4-(3-甲氧基丙氧基)-3-甲基吡啶-2-基]甲基亚磺酰基}-1H-苯并咪唑钠盐，雷贝拉唑）和一种黏膜保护药物（香叶基香叶基丙酮，GGA）对胃溃疡的影响。与对照组相比，雷贝拉唑（30mg/kg体重，皮下注射，每天一次，共六周）抑制胃酸分泌显著增加了胃溃疡的形成。相反，GGA治疗（100mg/kg体重，口服六周）显著抑制了溃疡的形成。在这些突变小鼠中观察到胆汁反流，并且它们的胃窦没有周期性强烈收缩。这些结果表明，胃窦运动紊乱导致的胆汁反流是W/Wv小鼠自发性胃溃疡的一个原因。
