Temporal relationship between cyclooxygenase inhibition, as measured by prostacyclin biosynthesis, and the gastrointestinal damage induced by indomethacin in the rat.
Temporal relationship between cyclooxygenase inhibition, as measured by prostacyclin biosynthesis, and the gastrointestinal damage induced by indomethacin in the rat.
复制标题
通过前列环素生物合成测量的环氧合酶抑制与大鼠吲哚美辛引起的胃肠道损伤之间的时间关系。
DOI：
10.5555/uri:pii:0016508581901967
复制
发表时间：
1981
期刊：
影响因子：
29.4
通讯作者：
B. Whittle
中科院分区：
文献类型：
--
作者：
B. Whittle
以体外产生前列环素(PGI2)作为前列腺素生物合成的指标，研究了皮下注射消炎痛对大鼠小肠和胃粘膜环氧合酶的抑制作用。这与肠道病变和胃侵蚀的形成进行了比较。吲哚美辛对胃粘膜前列环素的形成有明显的抑制作用，并伴随着胃糜烂的发展，但48h后对环氧合酶和胃糜烂的抑制作用不再明显。前列腺素抑制与小肠病变的形成之间没有这种时间关系，因为病变在环氧合酶抑制已经减弱的情况下从宏观上看是明显的和发展的。阿司匹林可延长对小肠环氧合酶活性的抑制，但不会对肠道造成损害。因此，仅抑制前列腺素合成可能不足以启动最终导致肠道损伤的过程。吲哚美辛影响肠道损伤的前列腺素非依赖性过程尚不清楚。
Inhibition of cyclooxygenase in the rat small intestine and gastric mucosa after subcutaneous administration of indomethacin has been investigated using prostacyclin (PGI2) production ex vivo as an index of prostaglandin biosynthesis. This has been compared with the formation of intestinal lesions and gastric erosions. Indomethacin caused marked inhibition of prostacyclin formation in the gastric mucosa, and this was accompanied by the development of gastric erosions, although after 48 h both inhibition of cyclooxygenase and gastric erosions were no longer apparent. There was no such temporal relationship between prostaglandin inhibition and the formation of lesions in the small intestine since the lesions became macroscopically apparent and developed at a time when cyclooxygenase inhibition was already declining. Aspirin caused a prolonged inhibition of small-intestinal cyclooxygenase activity, yet failed to cause intestinal damage. Thus, inhibition of prostaglandin synthesis alone may not be sufficient to initiate the processes which ultimately result in intestinal lesions. The prostaglandin-independent processes affected by indomethacin which lead to intestinal damage are as yet unknown.