目的 应用人胎盘体外循环灌注模型,进行格列本脲治疗妊娠期糖尿病的安全性研究。方法 选用自然分娩或剖宫产刚娩出的健康、完整、足月人胎盘36例,以安替比林为参照物,体外模拟子宫环境,建立同一个胎盘小叶母体面和子体面的双向闭合循环。每例胎盘体外循环灌注时间3 h,期间从母体池和子体池取样,应用UFLC-MS/MS测定格列本脲浓度。在循环过程中,通过检测灌流液pH值、pO2、hCG、葡萄糖消耗量、乳酸生成量、子体池损耗和安替比林的透过率来评估胎盘活性。结果 3 h循环灌注后,格列本脲的胎盘透过率为(1.64±0.85)%(n=36),清除指数为(0.05±0.03)(n=36)。结论 格列苯脲的胎盘透过率极低。对于妊娠期糖尿病患者,尤其是无法或拒绝胰岛素治疗的妊娠期糖尿病患者,格列本脲或可成为一种供选择的治疗药物。
Abstract
OBJECTIVE To determine the ex vivo human placental transfer of glyburide from maternal circulation to the fetal circulation in Chinese Hans population. METHODS Perfusion studies were performed on thirty-six placentas from healthy term pregnancies. The circulation of mother-placenta-fetus was set up ex vivo within minutes and accessed by studying spectrometry. Integrity and viability of the placenta were determined by measuring fetal volume loss, pH, pO2, ΔhCG, glucose consumption and lactate production during the perfusion experiments. RESULTS Following 3 h of perfusion, the fetal transfer rate of glyburide was (1.64±0.85)%. The clearance index of glyburide was (0.05±0.03). CONCLUSION These data suggest that tiny amount of glyburide can cross the human placenta. Glyburide could be used as a clinically effective alternative to insulin therapy.
关键词
格列本脲 /
妊娠 /
妊娠期糖尿病 /
胎盘转运 /
体外人胎盘灌注模型
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Key words
glyburide /
pregnancy /
gestational diabetes mellitus /
transplacental transfer /
ex vivo human placenta perfusion model
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中图分类号：
R965
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参考文献
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脚注
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基金
云南省科技厅—昆明医科大学应用基础研究联合专项重点项目资助;云南省卫生科技计划项目资助(2017NS070);云南省高层次卫生计生技术人才培养专项经费资助(L-201614,H2017050,H2017051,H2017053)
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