Salhab A S, DeVane C L, Medrano T, Buhi W C, Tebbett I R, Shiverick K T
Department of Pharmacology & Therapeutics, University of Florida, Gainesville.
J Pharmacol Exp Ther. 1994 Jul;270(1):392-8.
This study evaluated the effects of chronic exposure to cocaine during pregnancy on the morphology and function of the placenta. Pregnant rats received either 45 or 60 mg/kg of cocaine hydrochloride by i.p. injection as a divided daily dose on days 8 to 18 of gestation. The maternal weight gain decreased by 20% to 24% (P < .05) in the two cocaine treatment groups, whereas the placental weight was not significantly altered. Fetal growth showed a dose-related decrease in the 45- and 60-mg/kg cocaine treatment groups; fetal body weights and length were significantly decreased by 5% to 10%. The plasma levels of cocaine were 0.79 and 1.09 micrograms/ml in the 45- and 60-mg treatment dose groups, respectively; the level in the fetal plasma was 3-fold higher in the latter group. Placental tissue explants were cultured in the presence of [35S]-methionine to investigate whether cocaine exposure altered placental protein synthesis. Secreted proteins were analyzed by polyacrylamide gel electrophoresis followed by fluorography or by western blotting and immunostaining with antibodies to placental prolactin-like proteins-B and -C and growth hormone-related protein-1. The data showed that there were no quantitative or qualitative changes in placental peptide hormone secretion as a result of the cocaine treatment. These data indicate that chronic cocaine exposure in the pregnant rat is associated with fetal growth retardation in the absence of alterations in placental morphology or secretory protein synthesis.
本研究评估了孕期长期接触可卡因对胎盘形态和功能的影响。在妊娠第8至18天,怀孕大鼠每天腹腔注射45或60mg/kg盐酸可卡因,分剂量给药。两个可卡因治疗组的母体体重增加减少了20%至24%(P<.05),而胎盘重量没有显著变化。在45mg/kg和60mg/kg可卡因治疗组中,胎儿生长呈剂量相关下降;胎儿体重和体长显著下降了5%至10%。45mg和60mg治疗剂量组的可卡因血浆水平分别为0.79和1.09μg/ml;后一组胎儿血浆中的水平高出3倍。在[35S]-蛋氨酸存在的情况下培养胎盘组织外植体,以研究接触可卡因是否会改变胎盘蛋白质合成。分泌蛋白通过聚丙烯酰胺凝胶电泳,随后进行荧光自显影分析,或通过蛋白质印迹法以及用针对胎盘催乳素样蛋白-B和-C以及生长激素相关蛋白-1的抗体进行免疫染色来分析。数据显示,可卡因治疗后胎盘肽激素分泌没有定量或定性变化。这些数据表明,怀孕大鼠长期接触可卡因与胎儿生长迟缓有关,而胎盘形态或分泌蛋白合成没有改变。