Randall C L, Ekblad U, White N M, Cook J L
Department of Psychiatry and Behavioral Sciences, Medical University of South Carolina, Charleston 29425, USA.
Alcohol Clin Exp Res. 1996 Nov;20(8):1321-8. doi: 10.1111/j.1530-0277.1996.tb01129.x.
Studies from our laboratory indicate that prostaglandins may be mediators of at least some of the teratogenic actions of ethanol in both mouse and human tissue model systems. The present studies were designed to evaluate the relationship between ethanol and prostaglandin E (PGE) production in isolated human placental cotyledons. Placentas were obtained immediately after cesarean section delivery. A fetal artery supplying a single cotyledon was identified and cannulated, and the isolated cotyledon was placed in a perfusion chamber where maternal circulation was established and dual circulation continued throughout the perfusion procedure. Antipyrine clearance, oxygen consumption, and placental production of human chorionic gonadotropin were measured to verify tissue viability. PGE levels of the perfusate were measured by radioimmunoassay. Study 1 evaluates the effect of perfusion with 25 and 100 mM ethanol on placental PGE production. It was found that PGE production increased after perfusion with 25 mM ethanol, but not during the perfusion period per se. The paradigm for study 2 was identical to that of study 1, with the addition of a buffer washout period after 100-mM ethanol perfusion. Again, results indicate that perfusate PGE levels were increased in the buffer washout periods after the 25-mM and the 100-mM ethanol perfusions. The effect was not concentration dependent. An increase in circulating PGE associated with ethanol administration may be teratogenic actions and represent a potential mechanism underlying at least some aspects of fetal alcohol syndrome.
我们实验室的研究表明，在小鼠和人体组织模型系统中，前列腺素可能是乙醇至少部分致畸作用的介质。本研究旨在评估乙醇与离体人胎盘小叶中前列腺素E（PGE）产生之间的关系。胎盘在剖宫产分娩后立即获取。识别并插管一条为单个小叶供血的胎儿动脉，将离体小叶置于灌注室中，在其中建立母体循环，并在整个灌注过程中维持双循环。测量安替比林清除率、耗氧量和人绒毛膜促性腺激素的胎盘产生量，以验证组织活力。通过放射免疫测定法测量灌注液中的PGE水平。研究1评估用25 mM和100 mM乙醇灌注对胎盘PGE产生的影响。发现用25 mM乙醇灌注后PGE产生增加，但在灌注期间本身并未增加。研究2的模式与研究1相同，在100 mM乙醇灌注后增加了一个缓冲液洗脱期。同样，结果表明，在25 mM和100 mM乙醇灌注后的缓冲液洗脱期，灌注液PGE水平升高。该效应不依赖于浓度。与乙醇给药相关的循环PGE增加可能具有致畸作用，并代表胎儿酒精综合征至少某些方面的潜在机制。
