Tiboni G M, Iammarrone E, Piccirillo G, Liberati M, Bellati U
Clinica Ginecologica e Ostetrica, Facoltà di Medicina e Chirurgia, Universita G. d'Annunzio, Chieti, Italy.
Am J Obstet Gynecol. 1998 Feb;178(2):270-9. doi: 10.1016/s0002-9378(98)80012-4.
Our purpose was to investigate the effect of aspirin pretreatment on hyperthermia-induced teratogenesis. The rationale for the study was based on the growing evidence that prostaglandin pathway may be involved in the cellular response to the thermic injury.
On gestation day 8.5 Swiss mice were treated with 0 or 200 mg/kg of aspirin and 1 hour later exposed to a single 10-minute thermostatic bath treatment at 38 degrees C, 41 degrees C, 42 degrees C, or 43 degrees C. On gestation day 18 uterine contents were evaluated for developmental disorders, including prenatal mortality, intrauterine growth restriction, and external, visceral, and skeletal abnormalities.
Consistent with expectations, hyperthermia impaired morphogenesis in a dose-related manner. Although aspirin alone did not reveal embryotoxicity, its administration potentiated hyperthermia-induced teratogenesis. A statistically significant interaction (p < 0.05) was observed at 42 degrees C, where the incidence of fetuses per litter with axial skeletal malformations increased from 20.3% to 55.7%.
A nonteratogenic dose of aspirin enhanced the teratogenic response to hyperthermia. This result fits the hypothesis that prostaglandins may play a protective role in hyperthermia-induced teratogenesis.
我们的目的是研究阿司匹林预处理对高温诱导致畸的影响。该研究的理论依据是，越来越多的证据表明前列腺素途径可能参与细胞对热损伤的反应。
在妊娠第8.5天，给瑞士小鼠分别注射0或200mg/kg的阿司匹林，1小时后将其置于38℃、41℃、42℃或43℃的恒温浴中处理10分钟。在妊娠第18天，评估子宫内容物的发育障碍，包括产前死亡率、宫内生长受限以及外部、内脏和骨骼异常。
与预期一致，高温以剂量相关的方式损害形态发生。虽然单独使用阿司匹林未显示胚胎毒性，但其给药增强了高温诱导的致畸作用。在42℃时观察到具有统计学意义的相互作用（p<0.05），此时每窝有轴向骨骼畸形胎儿的发生率从20.3%增加到55.7%。
非致畸剂量的阿司匹林增强了对高温致畸的反应。这一结果符合前列腺素可能在高温诱导致畸中起保护作用的假说。
