甲氨蝶呤对大鼠体内小肠前列腺素E2、D2和I2释放的影响。
Effect of methotrexate on the release of prostaglandins E2, D2, and I2 from small intestine in the rat in vivo.
作者信息
Weiler H, Moser U, Gerok W
机构信息
Department of Internal Medicine, University of Freiburg, Federal Republic of Germany.
出版信息
J Cancer Res Clin Oncol. 1990;116(6):629-32. doi: 10.1007/BF01637085.
Intraperitoneal administration of methotrexate in a single dose of 40 mg/kg induces fluid accumulation in the small intestine of rats, significantly increasing jejunal PGE2 formation and simultaneously the amounts of PGE2 in the intestinal contents in vivo. Concomitantly, jejunal PGD2 and 6-keto-PGF1 alpha generation and the amounts of these prostaglandins in the intestinal contents were significantly lowered. However, PGD2 and 6-keto-PGF1 alpha jejunal release, and the amounts of these prostaglandins found in the intestinal contents, were already low after a sublethal dose (4 mg/kg) of methotrexate, whereas the jejunal release as well as the amounts in the intestinal contents of PGE2 were not altered. Fluid accumulation, the amounts of prostaglandins in the intestinal contents and jejunal release of prostaglandins are significantly inhibited by indomethacin. The increased jejunal synthesis of PGE2, with its enteropooling effect, may play a significant role in methotrexate-induced diarrhea in rats.
腹腔注射单剂量40mg/kg的甲氨蝶呤会在大鼠小肠中诱导液体蓄积，显著增加空肠中前列腺素E2（PGE2）的生成，同时体内肠内容物中PGE2的量也会增加。与此同时，空肠中前列腺素D2（PGD2）和6-酮-前列腺素F1α（6-keto-PGF1α）的生成以及这些前列腺素在肠内容物中的量会显著降低。然而，在亚致死剂量（4mg/kg）的甲氨蝶呤作用后，空肠中PGD2和6-keto-PGF1α的释放以及在肠内容物中发现的这些前列腺素的量已经很低，而空肠中PGE2的释放以及肠内容物中PGE2的量并未改变。吲哚美辛可显著抑制液体蓄积、肠内容物中前列腺素的量以及空肠中前列腺素的释放。空肠中PGE2合成增加及其肠内积液作用可能在甲氨蝶呤诱导的大鼠腹泻中起重要作用。
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