胎盘转运大鼠模型的改进及在丙泊酚研究中的应用  

A modified rat model for the study on transplacental transfer of propofol

作　　者：吕卓辰[1] 许玲美[2,3] 檀琼[2,3] 秦燕[2,3] 于布为[1] 

机构地区：[1]上海交通大学医学院附属瑞金医院麻醉科,上海200025 [2]上海医药工业研究总院 [3]上海医药工业研究院创新药物与制药工艺国家重点实验室

出　　处：《上海医学》2014年第2期131-134,共4页Shanghai Medical Journal

基　　金：国家自然科学基金资助项目(81371219、81072703)

摘　　要：目的研究丙泊酚在妊娠大鼠的胎盘转运（TPT）情况。方法6只成功受孕的Sprague—Dawley大鼠。在妊娠第20天经母鼠尾静脉注射10mg／kg丙泊酚，注射后15和120min，采用内眦静脉取血法采集母鼠全血（母鼠组），断头取血法采集胎鼠全血（胎鼠组），测定pH值、动脉血二氧化碳分压（PaCO2）、动脉血氧分压（PaO2）和动脉血氧饱和度（SaO2）；在丙泊酚注射后3～150min时间段内，采用高效液相色谱串联质谱法（LC-MS／MS）测定母鼠和胎鼠的丙泊酚血药浓度。结果注射丙泊酚后15min时，母鼠组的PaO2显著高于同组基础值（P〈0．05），而胎鼠组不同时间点的差异均无统计学意义（P值均〉0．05）。母鼠组的丙泊酚血药浓度在给药后3min达峰值，以后逐步下降（趋势P〈0．01）；胎鼠组的丙泊酚血药浓度在给药后15min达峰值，以后逐步下降（趋势P〈0．01）。胎鼠组在给药后3、5min时的丙泊酚血药浓度显著低于母鼠组同时间点（P值均〈0．05），其余时间点间的差异均无统计学意义（P值均〉0．05）。结论本研究简化了TPT模型的全血采集方法，缩短了给药后的采样间隔时间，操作方法切实可行，成功率高，能够满足对丙泊酚等体内快速代谢的麻醉药物TPT研究的需要。首次实现了妊娠大鼠中丙泊酚的TPT血药浓度测定，为在小动物中研究麻醉药物TPT情况提供了方法学依据。Objective To report a modified rat model applicable for the study on transplacental transfer （TPT） of propofol. Methods Six pregnant Sprague-Dawley rats on gestational day 20 were given propofol （10 mg/kg） via tail vein. Maternal and fetal blood samples were collected by angular vein and decapitation, respectively. The pH value, arterial partial pressure of carbon dioxide （PaCO2）, arterial partial pressure of oxygen （PaO2） and arterial oxygen saturation （SaO2） were measured at 15 min and 120 min after propofol injection. Maternal and fetal propofol plasma concentrations were monitored by liquid chromatography-tandem mass spectrometry （LC-MS/MS） in 3- 150 min after propofol administration. Results The level of PaO2 at 15 min after propofol injection was significantly higher than the baseline in maternal rats （ P〈0.05）, while there was no significant difference in PaO2 before and after propofol injection in fetal rats （all P〉0.05）. Maternal propofol concentration reached the peak at 3 min after injection and decreased gradually （P for trend〈0.01 ）. On the other hand, the fetal kinetic profile demonstrated a gradual increase before reaching the peak at 15 min, and then the concentration declined slowly over 150 min （ P for trend〈0.01 ）. Fetal propofol plasma concentrations at 3 min and 5 min after injection were significantly lower than maternal ones （both P〈0.05）. Conclusion The procedure of blood collection is simplified and sampling interval is shortened in our study. The modified rat model can be satisfactorily used for the pharmacokinetic study on TPT of anesthetics. We demonstrate the TPT information of propofol in pregnant rats for the first time and provide the basic evidence for the further study of TPT in small animal model.

关 键 词：胎盘转运 妊娠大鼠 丙泊酚 母鼠 胎鼠 

分 类 号：R614[医药卫生—麻醉学]