Takeuchi K, Nishiwaki H, Ishihara Y, Okabe S
Department of Applied Pharmacology, Kyoto Pharmaceutical University, Japan.
Jpn J Pharmacol. 1987 Jul;44(3):269-81. doi: 10.1254/jjp.44.269.
The present study was undertaken using acetazolamide (AZ) and cysteamine (Cys) to investigate the relationship between gastric motor activity and the phenomenon of "cytoprotection" in rats. Both AZ (10-100 mg/kg) and Cys (10-100 mg/kg), given either p.o. or s.c., significantly reduced the formation of gastric mucosal injury caused by HCl-ethanol (1 ml of 60% ethanol in 150 mM HCl, p.o.). The protective effect of Cys appeared within 10 min, reached the maximal levels 30 min later, while that of AZ appeared from 30 min after administration and became potent with a latency period after treatment. Neither indomethacin (IM: 5 mg/kg, s.c.) nor N-ethylmaleimide (NEM: 5 mg/kg, s.c.) significantly affected the protective effect of Cys, whereas that of AZ was almost totally antagonized by IM. Both AZ and Cys, given either intragastrically or s.c., significantly inhibited gastric motor activity measured as intraluminal pressure recordings, but had minimal effect on acid and alkaline secretion. IM significantly attenuated the inhibitory effect of AZ on the motor activity, while NEM did not affect the inhibited motor responses caused by AZ and Cys. A significant relationship was found between the inhibitory effects of these two drugs on gastric motor activity and HCl-ethanol-induced mucosal injury, the correlation coefficient being 0.819 (P less than 0.01). When the mucosal folds were visualized with Gentian Violet (1 ml of 0.5% v/v, p.o.), both AZ and Cys significantly prevented the localized staining along the mucosal folds, suggesting dissolution of the folds. These results suggest that both AZ and Cys protect the gastric mucosa against injury caused by HCl-ethanol, probably through a dissolution of mucosal folds due to inhibition of gastric motor activity.
本研究采用乙酰唑胺（AZ）和半胱胺（Cys）来研究大鼠胃运动活性与“细胞保护”现象之间的关系。口服或皮下注射给予AZ（10 - 100mg/kg）和Cys（10 - 100mg/kg），均能显著减少由盐酸 - 乙醇（1ml含60%乙醇的150mM盐酸，口服）引起的胃黏膜损伤。Cys的保护作用在10分钟内出现，30分钟后达到最大水平，而AZ的保护作用在给药后30分钟出现，并在治疗后有一个潜伏期才变得显著。吲哚美辛（IM：5mg/kg，皮下注射）和N - 乙基马来酰亚胺（NEM：5mg/kg，皮下注射）均未显著影响Cys的保护作用，而AZ的保护作用几乎完全被IM拮抗。口服或皮下注射给予AZ和Cys，均能以腔内压力记录来衡量显著抑制胃运动活性，但对胃酸和碱分泌影响极小。IM显著减弱了AZ对运动活性的抑制作用，而NEM不影响AZ和Cys引起的运动反应抑制。发现这两种药物对胃运动活性的抑制作用与盐酸 - 乙醇诱导的黏膜损伤之间存在显著关系，相关系数为0.819（P小于0.01）。当用龙胆紫（1ml 0.5% v/v，口服）使黏膜皱襞可视化时，AZ和Cys均能显著防止沿黏膜皱襞的局部染色，提示皱襞溶解。这些结果表明，AZ和Cys可能通过抑制胃运动活性导致黏膜皱襞溶解，从而保护胃黏膜免受盐酸 - 乙醇引起的损伤。
