人类胎盘体外循环灌注模型的建立  

Establishment of human placental perfusion model

作　　者：黄桦[1] 张峻[1] 马润玫[2] 闫晨[1] 郑巧玲[1] 姚勤[1] 

机构地区：[1]昆明医科大学第一附属医院临床药学科,云南昆明650032 [2]昆明医科大学第一附属医院妇产科,云南昆明650032

出　　处：《中国药理学与毒理学杂志》2013年第6期1014-1019,共6页Chinese Journal of Pharmacology and Toxicology

基　　金：云南省应用基础研究课题(2008ZC128M);"紫禁城药师国际论坛"科研课题~~

摘　　要：目的 建立人类胎盘体外循环灌注模型。方法 体外模拟子宫环境，以安替比林为参照物，选用自然分娩或剖宫产刚娩出的健康、完整、足月的人类胎盘，在其胎儿面选择供应同一胎盘小叶的一对脐动静脉，穿刺插管后建立单个胎盘小叶的胎儿循环；胎儿面向下固定于胎盘室内，放置于37℃恒温水浴中，将一端接有导管的两根钝头针插入同一胎盘小叶的绒毛间隙内2~3 mm，建立母体循环。以蠕动泵为循环动力，向同一胎盘小叶的母体侧和胎儿侧供应胎盘灌流液，建立同一个胎盘小叶母体和胎儿双向闭合循环。在母体池中加入安替比林100 mg·L-1，循环灌注3 h。测定胎儿循环侧液体的渗漏率；采用高效液相色谱法于循环开始0，5，10，15，20，30，45，60，75，90，105，120，150和180 min测定安替比林的浓度计算胎盘透过率，并测定循环开始后0，30，60，90，120，150和180 min母体池和胎儿池中的胎盘灌流液的pH值。结果本研究成功建立人类胎盘体外循环灌注模型20例。在持续循环的3 h过程中，母体池和胎儿池灌流液pH值均维持在7.2~7.4范围内；胎儿侧漏液率为（2.47±1.27）ml·h-1；循环结束时，阳性标记物安替比林的胎盘透过率为（36.62±5.08）%。结论 本研究建立的人类胎盘体外循环灌注模型可用于药物的胎盘透过性研究，为妊娠期用药安全性提供可靠的体外研究模型和理论支持。OBJECTIVE To establish the human placental perfusion model. METHODS The intact placentas were obtained from term pregnancies either after vaginal or cesarean delivery. After tissue collection, a fetal vein-artery pair supplying a well defined cotyledon was identified. The fetal vessels were cannulated,and the flow of perfusate was established. The lobule was clamped with the fetal side downward into a chamber. Perfusion of the maternal side began with insertion of blunt-tipped needles into the intervillous space 2-3 mm below the decidual surface. The fetal and maternal circulations were independently controlled by roller pumps. The circulation of mother-placenta-fetus was set up in vitro within minutes and accessed by studying antipyrine. A loss from the fetal reservoir was determined. The circulation of mother-placenta-fetus was set up in vitro within minutes and for 3 h. Antipyrine 100 mg·L-1 was added in maternal reservoir. Antipyrine in fetal reservoir was determined by using high-performance liquid chromatograph method at 0,5,10,15,20,30,45,60,75,90,105,120,150 and 180 min from the beginning. A loss from the fetal reservoir was measured and the pH from the maternal reservoir and the fetal reservoir was monitored each 30 min. RESULTS Twenty human placental perfusion models were built successfully. During the perfusion, pH was monitored each 30 min from maternal reservoir and fetal reservoir and was always in the range 7.2-7.4. A loss from the fetal reservoir was（2.47±1.27）ml·h-1 and placental antipyrine transfer rate was（36.62±5.08）% at the end of the perfusion. CONCLUSION The human placental perfusion model established can be used to predict placental drug transfer, which can be a reliable tool to study human placental transfer of drugs and can be useful for assessing drug therapy risks and benefits during pregnancy.

关 键 词：人类胎盘体外循环灌注模型 转运 安替比林 

分 类 号：R-332[医药卫生]