Uchida M, Hamura H, Takagi S, Noguchi Y, Shibata H, Honda H
Research Laboratories, Grelan Pharmaceutical Co., Ltd., Tokyo, Japan.
Nihon Yakurigaku Zasshi. 1994 Mar;103(3):111-20. doi: 10.1254/fpj.103.111.
Gastric lesion was induced by the oral administration of acidified aspirin in rats with hepatic cirrhosis produced by N-nitrosodiethylamine (NDA) or carbon tetrachloride (CCl4). Gastric lesion by acidified aspirin was aggravated in NDA-induced cirrhosis, but not in CCl4-cirrhotic rats. To clarify this difference in the susceptibility of the gastric mucosa, gastric mucosal blood flow and gastric emptying were measured by the hydrogen gas clearance method and beads method, respectively. Gastric mucosal blood flow was lower and gastric emptying was significantly delayed in NDA-induced cirrhotic rats as compared with the controls, but not in CCl4-induced cirrhotic rats. Gastric mucosal blood flow in NDA-induced cirrhotic rats was significantly decreased by the oral administration of acidified aspirin as compared with the controls. Aldioxa dose-dependently inhibited the gastric lesion formation by acidified aspirin and inhibited the decrease of gastric mucosal blood flow in NDA-induced cirrhotic rats. These results suggest that aggravation of gastric lesion induced by acidified aspirin in NDA-induced cirrhotic rats would be due to the decrease of gastric mucosal blood flow and delay of gastric emptying. In addition, aldioxa showed a protective effect against gastric lesions induced by acidified aspirin in NDA-induced cirrhotic rats, suggesting that this compound would have an inhibitory effect on gastric lesions that are accompanied by hepatic cirrhosis.
通过给用N-亚硝基二乙胺(NDA)或四氯化碳(CCl4)诱导肝硬化的大鼠口服酸化阿司匹林来诱发胃损伤。在NDA诱导的肝硬化大鼠中,酸化阿司匹林所致的胃损伤加重,但在CCl4诱导的肝硬化大鼠中并非如此。为了阐明胃黏膜易感性的这种差异,分别用氢气清除法和珠子法测量胃黏膜血流量和胃排空情况。与对照组相比,NDA诱导的肝硬化大鼠胃黏膜血流量较低,胃排空明显延迟,但CCl4诱导的肝硬化大鼠并非如此。与对照组相比,给NDA诱导的肝硬化大鼠口服酸化阿司匹林后,其胃黏膜血流量显著降低。阿尔多沙剂量依赖性地抑制酸化阿司匹林所致的胃损伤形成,并抑制NDA诱导的肝硬化大鼠胃黏膜血流量的降低。这些结果表明,NDA诱导的肝硬化大鼠中酸化阿司匹林所致胃损伤加重可能是由于胃黏膜血流量减少和胃排空延迟。此外,阿尔多沙对NDA诱导的肝硬化大鼠中酸化阿司匹林所致胃损伤具有保护作用,表明该化合物对伴有肝硬化的胃损伤具有抑制作用。