Hayles C D, Andrews F J, O'Brien P E
Department of Surgery, Monash Medical School, Alfred Hospital, Prahran, Victoria, Australia.
J Gastroenterol Hepatol. 1998 Jun;13(6):572-8. doi: 10.1111/j.1440-1746.1998.tb00692.x.
Increasing evidence suggests that non-steroidal anti-inflammatory drugs (NSAID) differ in gastrotoxicity. This study aimed to compare the effects of a short-acting NSAID, tiaprofenic acid, with indomethacin on experimental gastric ulcer healing in a rat model. Similar anti-inflammatory and prostaglandin-inhibitory doses of indomethacin (1 mg/kg) and tiaprofenic acid (2 mg/kg) were administered to rats with acetic acid-induced ulcers. After 2 weeks treatment, rats were killed and ulcer size determined. In addition, histological sections of ulcers were assessed for ulcer contraction and mucosal regeneration. The degree of inhibition of prostaglandin E2 (PGE2) synthesis was 72% at 2 h after tiaprofenic acid and 64% at 2 h after indomethacin administration, respectively. Rats treated with indomethacin for 2 weeks had significantly larger ulcers, both macroscopically and microscopically, than controls. Rats treated with tiaprofenic acid for 2 weeks had ulcers of a similar size to those of controls. Indomethacin-treated ulcers showed a failure in mucosal regeneration. Tiaprofenic acid-treated ulcers had significantly more regeneration than indomethacin-treated ulcers. We conclude that tiaprofenic acid inhibits mucosal prostaglandin levels but does not inhibit experimental gastric ulcer healing. These findings suggest that inhibition of PGE2 synthesis is not the only factor in generating gastrotoxicity and that a shift to low gastrotoxic NSAID may be clinically worthwhile.
越来越多的证据表明，非甾体抗炎药（NSAID）在胃毒性方面存在差异。本研究旨在比较短效NSAID噻洛芬酸与吲哚美辛对大鼠实验性胃溃疡愈合的影响。将吲哚美辛（1 mg/kg）和噻洛芬酸（2 mg/kg）的相似抗炎和前列腺素抑制剂量给予乙酸诱导溃疡的大鼠。治疗2周后，处死大鼠并测定溃疡大小。此外，评估溃疡的组织学切片的溃疡收缩和黏膜再生情况。噻洛芬酸给药后2小时前列腺素E2（PGE2）合成的抑制程度分别为72%，吲哚美辛给药后2小时为64%。用吲哚美辛治疗2周的大鼠，无论在宏观还是微观上，溃疡都明显大于对照组。用噻洛芬酸治疗2周的大鼠溃疡大小与对照组相似。吲哚美辛治疗的溃疡显示黏膜再生失败。噻洛芬酸治疗的溃疡比吲哚美辛治疗的溃疡有明显更多的再生。我们得出结论，噻洛芬酸抑制黏膜前列腺素水平，但不抑制实验性胃溃疡愈合。这些发现表明，抑制PGE2合成不是产生胃毒性的唯一因素，转向低胃毒性的NSAID在临床上可能是值得的。
