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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
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DOI:
作者:
吕卓辰,许玲美,檀琼,秦燕,于布为
LU Zhuochen, XU Lingmei, TAN Qiong, QIN Yan, YU Buwei
作者单位:
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,上海 200040
aDepartment of Anesthesiology, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China; State Key Laboratory of New Drug and Pharmaceutical Process, Shanghai Institute of Pharmaceutical Industry, China State Institute of Pharmaceutical Industry, Shanghai, China
关键词:
胎盘转运;妊娠大鼠;丙泊酚;母鼠;胎鼠
Transplacental transfer; Rat model; Propofol; Maternal rats; Fetal rats
摘要:
目的 对Varma等建立的妊娠大鼠胎盘转运(Transplacental Transfer,TPT)模型进行改进,在丙泊酚TPT研究中进行应用。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10 mg·kg-1丙泊酚,在给药后3 ~ 150 min时间内,采用内眦静脉取血法采集母鼠全血,采用断头取血法采集胎鼠全血,简化了采血方法,缩短了采样时间间隔。采用高效液相色谱串联质谱法(LC-MS/MS)测定母胎丙泊酚药物浓度。结果 成功对TPT模型进行改进,母鼠与胎鼠在实验前、给药后15 min和120 min均未出现明显的低氧血症和高碳酸血症。经母鼠尾静脉给药后,丙泊酚能够迅速通过胎盘屏障。在给药后3 ~ 150 min时间内,母鼠血药浓度持续下降,胎鼠血药浓度呈现先升后降的变化趋势,且从给药后30 min开始,胎鼠血药浓度高于母鼠。结论 本研究对Varma等的TPT模型进行改进,可行性强,成功率高。通过本模型,首次实现了妊娠大鼠中丙泊酚的TPT浓度测定,为在小动物中研究麻醉药物TPT研究提供了方法学依据。
Objective To report a modified rat model especially applicable for the study on transplacental transfer (TPT) of anesthetics. Methods The feasibility of our modified rat model was evaluated by propofol. Six pregnant Sprague-Dawley rats on gestational day 20 were all given propofol (10 mg·kg-1) via tail vein. Maternal and fetal blood samples were collected sequentially from 3 min to 150 min post injection. Simplified operation and reduced intervals were two major modifications in our model. Samples were assessed using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Results Zero mortality was observed within 150 min post propofol injection. The affects of concentrations caused by physiological changes was reduced to a minimum. With our model, we found that propofol can rapidly cross through the placenta. Maternal propofol plasma concentration demonstrated a steep decrease over 150 min post injection. On the other hand, the fetal kinetic profile demonstrated a gradual increase before reaching the peak at 15 min, and then declined slowly over 150 min. Conclusions The modified rat model can be satisfactorily used for the pharmacokinetic study on TPT of anesthetics, which could be used as a substitute for or a supplement to the pregnant ewe model. This model may further our knowledge on clinical application of anesthetics in pregnant women.
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