Klein K L, Clark K E, Scott W J
Prostaglandins. 1984 May;27(5):659-72. doi: 10.1016/0090-6980(84)90005-4.
Aspirin and salicylate are well-known but poorly understood teratogens in laboratory animals. Because aspirin inhibits PG synthesis, we systematically examined PG synthesis in rat embryo homogenates, the inhibition of PG synthesis in vivo and ex vivo by various non-steroidal anti-inflammatory drugs, and tested the hypothesis that the inhibition of PG synthesis is responsible for aspirin-induced limb defects in rats. We report that embryonic rat homogenates synthesize 6-keto-PGF1alpha, PGE, and PGF in large amounts from endogenous substrate, that aspirin and other non-steroidal anti-inflammatory drugs inhibit PG synthesis in vitro but not necessarily in vivo, and that contrary to our original hypothesis, the inhibition of PG synthesis is likely not responsible for aspirin-induced limb defects in rats.
阿司匹林和水杨酸盐在实验动物中是广为人知但却了解甚少的致畸剂。由于阿司匹林抑制前列腺素(PG)合成,我们系统地研究了大鼠胚胎匀浆中的PG合成、各种非甾体抗炎药在体内和体外对PG合成的抑制作用,并验证了PG合成受抑制是导致大鼠阿司匹林诱导肢体缺陷的原因这一假设。我们报告称,大鼠胚胎匀浆可从内源性底物大量合成6-酮-前列腺素F1α、前列腺素E和前列腺素F,阿司匹林和其他非甾体抗炎药在体外可抑制PG合成,但在体内不一定如此,而且与我们最初的假设相反,PG合成受抑制可能并非大鼠阿司匹林诱导肢体缺陷的原因。