Wang J Y, Yamasaki S, Takeuchi K, Okabe S
Department of Applied Pharmacology, Kyoto Pharmaceutical University, Japan.
Gastroenterology. 1989 Feb;96(2 Pt 1):393-402. doi: 10.1016/0016-5085(89)91563-1.
We examined the mechanism by which repeated administration of indomethacin significantly delays the natural healing of experimental gastric ulcers induced in rats. Gastric ulcers were produced 5 days after injecting 20% acetic acid (0.03 ml) into the submucosal layer of the gastric wall of the antral-oxyntic border. The natural healing of the acetic acid-induced ulcers was extensively delayed by administering indomethacin (1 mg/kg) subcutaneously once daily for 2 or 4 wk. Subcutaneous administration of natural prostaglandin E2 (1 or 3 mg/kg) twice daily for 2 and 4 wk, together with indomethacin, significantly prevented the delay of ulcer healing. Prostaglandin E2 (3 mg/kg) administered twice daily for 2 wk also significantly accelerated the natural healing of the ulcers. A single administration of prostaglandin E2 (1 or 3 mg/kg) significantly reduced histamine-stimulated gastric acid secretion for 4 h in acute fistula rats with 1- or 2-wk-old ulcers, treated with or without daily indomethacin (1 mg/kg). Endogenous prostaglandin E2 levels in the gastric mucosa of normal rats were significantly reduced for at least 12 h after a single or repeated administration of indomethacin (1 mg/kg) for 2 or 4 wk. Gastric mucosal prostaglandin E2 levels in rats with ulcers (5 days after acetic acid injection) were also markedly reduced by indomethacin. This reduction significantly reverted toward control levels after administration of exogenous prostaglandin E2 (3 mg/kg). These results suggest that endogenous prostaglandin E2 plays an important role in the healing process of gastric ulcers.
我们研究了反复给予吲哚美辛显著延迟大鼠实验性胃溃疡自然愈合的机制。在胃窦-泌酸腺交界处胃壁黏膜下层注射20%乙酸（0.03 ml）5天后制备胃溃疡。通过每天皮下注射吲哚美辛（1 mg/kg）持续2或4周，乙酸诱导的溃疡自然愈合被广泛延迟。在给予吲哚美辛的同时，每天皮下注射天然前列腺素E2（1或3 mg/kg）两次，持续2和4周，可显著防止溃疡愈合延迟。每天两次给予前列腺素E2（3 mg/kg）持续2周也显著加速了溃疡的自然愈合。在患有1或2周龄溃疡的急性瘘管大鼠中，无论是否每日给予吲哚美辛（1 mg/kg），单次给予前列腺素E2（1或3 mg/kg）均可显著降低组胺刺激的胃酸分泌4小时。在单次或反复给予吲哚美辛（1 mg/kg）2或4周后，正常大鼠胃黏膜中的内源性前列腺素E2水平至少12小时显著降低。吲哚美辛也显著降低了溃疡大鼠（乙酸注射后5天）的胃黏膜前列腺素E2水平。给予外源性前列腺素E2（3 mg/kg）后，这种降低显著恢复至对照水平。这些结果表明内源性前列腺素E2在胃溃疡愈合过程中起重要作用。
