胎盘转运大鼠模型的改进及在麻醉药物中的应用-应用昆虫学报.DOC

胎盘转运大鼠模型的改进及在丙泊酚研究中的应用 吕卓辰1，许玲美2，檀琼2，秦燕2，于布为1*（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） *通讯作者：于布为，上海交通大学医学院附属瑞金医院麻醉科，瑞金二路197号 E-mail地址： HYPERLINK mailto:yubuwei@ yubuwei_2013@126.com 【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。 【关键词】胎盘转运；妊娠大鼠；丙泊酚；母鼠；胎鼠 A Modified Rat Model for the Study on Transplacental Transfer of Propofol LU Zhuochen,a XU Lingmei,b TAN Qiong,b QIN Yan,b YU Buweia*. aDepartment of Anesthesiology, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China; bState Key Laboratory of New Drug and Pharmaceutical Process, Shanghai Institute of Pharmaceutical Industry, China State Institute of Pharmaceutical Industry, Shanghai, China *Correspondence to: YU Buwei, Department of Anesthesiology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Ruijin Er Road, Shanghai, China E-mail address: HYPERLINK mailto:yubuwei@ yubuwei_2013@126.com 【Abstract】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 mortali