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加氧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：
10.1016/0016-5085(81)90196-7
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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
使用离体前列环素 (PGI2) 产生作为前列腺素生物合成的指标，研究了皮下注射吲哚美辛后对大鼠小肠和胃粘膜中环氧合酶的抑制。这与肠道病变和胃糜烂的形成进行了比较。吲哚美辛显着抑制胃粘膜中前列环素的形成，并伴随着胃糜烂的发展，尽管48小时后环加氧酶的抑制和胃糜烂都不再明显。前列腺素抑制与小肠病变形成之间不存在这种时间关系，因为在环氧合酶抑制已经下降时，病变变得肉眼可见并发生。阿司匹林可长时间抑制小肠环氧合酶活性，但不会造成肠道损伤。因此，单独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。受吲哚美辛影响而导致肠道损伤的前列腺素独立过程尚不清楚。
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.