Kurebayashi Y, Ikeda T, Osada Y
Laboratory of Microbiology and Pathology, Research Institute, Daiichi Seiyaku Co., Ltd., Tokyo, Japan.
Jpn J Pharmacol. 1988 Jan;46(1):17-25. doi: 10.1254/jjp.46.17.
The protective effect of cetraxate, an antiulcer and antigastritis agent, on HCl.ethanol-induced gastric lesions was investigated in rats. Oral administration of 1 ml of HCl.ethanol (60% ethanol in 150 mM HCl) induced within 1 hr linear hemorrhagic necrosis in the gastric mucosa. Either oral or intraperitoneal treatment with cetraxate (30-300 mg/kg) significantly inhibited such macroscopic gastric lesions in a dose-related manner, and the inhibition at the oral highest dose (300 mg/kg) was practically complete. Histological analysis also confirmed that cetraxate effectively prevented deep mucosal necrosis, but showed that it was without protective effect on the surface epithelial disruption and submucosal edema in response to HCl.ethanol. The antilesion activity of cetraxate was of statistically significance for at least 3 hr after a single injection, and it was hardly affected by the removal of the gastric contents just prior to application of the necrotizing agent. However, subcutaneous treatment of rats with indomethacin (5 mg/kg) resulted in a partial but significant attenuation in the protection afforded by cetraxate, suggesting that dual mechanisms related and unrelated to endogenous prostaglandins may be involved in its protective activity. The results demonstrate that cetraxate is a potent cytoprotective agent effectively preventing the formation of gastric mucosal necrosis induced by HCl.ethanol.
研究了抗溃疡和抗胃炎药物西曲酸对盐酸 - 乙醇诱导的大鼠胃损伤的保护作用。口服1 ml盐酸 - 乙醇（150 mM盐酸中含60%乙醇）在1小时内可导致胃黏膜出现线性出血性坏死。西曲酸（30 - 300 mg/kg）口服或腹腔注射治疗均能以剂量相关的方式显著抑制此类肉眼可见的胃损伤，口服最高剂量（300 mg/kg）时的抑制作用几乎完全。组织学分析也证实西曲酸能有效预防深层黏膜坏死，但显示其对盐酸 - 乙醇所致的表面上皮破坏和黏膜下水肿无保护作用。西曲酸的抗损伤活性在单次注射后至少3小时具有统计学意义，且在应用坏死剂前清除胃内容物对其影响不大。然而，用吲哚美辛（5 mg/kg）皮下治疗大鼠会导致西曲酸提供的保护作用部分但显著减弱，这表明其保护活性可能涉及与内源性前列腺素相关和不相关的双重机制。结果表明，西曲酸是一种有效的细胞保护剂，能有效预防盐酸 - 乙醇诱导的胃黏膜坏死的形成。
