Lipton Jack W, Vu Toan Q, Ling Zaodung, Gyawali Sandeep, Mayer Jennifer R, Carvey Paul M
Department of Pharmacology, Rush Medical College of Rush University, Rush-Presbyterian-St. Luke's Medical Center, Chicago, IL 60612, USA.
Neurotoxicol Teratol. 2002 Mar-Apr;24(2):143-8. doi: 10.1016/s0892-0362(01)00209-4.
We have previously demonstrated that maternal cocaine injections result in a gradient of fetal brain cocaine levels that decrease as a function of the fetuses' proximity to the ovaries at embryonic (E) day 15. Our prior data suggest that cocaine-induced vasoconstriction may (1) limit cocaine's entry into the brain and (2) cause damage to DA neurons through injury associated with hypoxia or ischemia of the utero-placental junction. Therefore, using the microsphere technique (labeled with Ru(103)), the following study sought to determine whether the previously observed pattern of cocaine distribution among fetuses in the uterus were due to position-specific reductions in uterine or placental blood flow. On day 15, a single subcutaneous injection of 30 mg/kg cocaine HCl was administered to each rat. Thirty minutes after the cocaine injection, reference blood samples were drawn from the ventral tail artery. Uterine segments and placentae were removed and subjected to gamma counting. While results regarding placental blood flow were equivocal, cocaine significantly reduced average uterine blood flow by 54.6%. In addition, as one moves more proximal to the ovaries, cocaine progressively attenuates blood flow in uterine tissue segments. These data support the hypothesis that the pattern of drug distribution and subsequent brain alterations from prenatal cocaine exposure in our previous reports are likely due to differences in uterine blood flow.
我们之前已经证明，在胚胎（E）第15天，母体注射可卡因会导致胎儿脑内可卡因水平呈梯度变化，该梯度随着胎儿与卵巢距离的增加而降低。我们之前的数据表明，可卡因诱导的血管收缩可能（1）限制可卡因进入大脑，以及（2）通过与子宫 - 胎盘交界处缺氧或缺血相关的损伤对多巴胺能（DA）神经元造成损害。因此，本研究采用微球技术（用钌（103）标记），试图确定之前观察到的子宫内胎儿间可卡因分布模式是否是由于子宫或胎盘血流量的位置特异性减少所致。在第15天，给每只大鼠皮下注射一次30 mg/kg盐酸可卡因。注射可卡因30分钟后，从腹侧尾动脉采集参考血样。取出子宫段和胎盘并进行γ计数。虽然关于胎盘血流量的结果不明确，但可卡因使平均子宫血流量显著减少了54.6%。此外，随着位置向卵巢更近端移动，可卡因会使子宫组织段的血流量逐渐减少。这些数据支持了这样一种假设，即我们之前报告中产前可卡因暴露导致的药物分布模式及随后的脑改变可能是由于子宫血流量的差异所致。
