缺氧对重度子痫前期患者胎盘绒毛组织代谢足迹变化的影响

摘要

目的:探讨在不同氧浓度下体外培养正常妊娠孕妇及重度子痫前期患者胎盘绒毛组织培养液中代谢足迹的变化.方法:选择正常妊娠组(27例)及重度子痫前期组(27例)孕妇,在胎盘边缘、中间、近脐带处取绒毛组织,分别在1％氧浓度下及6％氧浓度下培养96小时,采用高效液相质谱色谱仪检测培养液中代谢产物,观察不同氧浓度下培养的绒毛组织代谢足迹的变化.结果:两组分别取自1％氧浓度和6％氧浓度下培养的同一胎盘边缘、中间、近脐带3点处胎盘绒毛组织代谢足迹的比较差异无统计学意义(P＞0.05)；1％氧浓度与6％氧浓度下培养的正常妊娠组胎盘绒毛组织代谢足迹比较,发现545个代谢物差异有统计学意义(P＜0.05)；1％氧浓度与6％氧浓度下培养的重度子痫前期组胎盘绒毛组织代谢足迹的比较差异无统计学意义(P＞0.05),1％氧浓度下培养的正常妊娠组与6％氧浓度下培养的重度子痫前期组胎盘绒毛组织代谢足迹的比较差异无统计学意义(P＞0.05).结论:缺氧可能影响胎盘绒毛组织的代谢,在重度子痫前期的发病机制中起重要作用,而利用高效液相质谱色谱仪的代谢组学技术能测定在不同氧浓度下培养的正常妊娠组和重度子痫前期孕妇胎盘绒毛组织代谢足迹的变化,表明该方法适合于重度子痫前期的代谢组学研究.%Objective: To explore the changes in the metabolic footprint in the culture medium with placen-tal villous explants got from normal pregnancy and severe preeclampsia at 1% or 6% oxygen tension. Methods :Placentas were obtained from normal pregnancies (re =27) and severe preeclampsia (re =27). Placentas were sampled at three stratified areas: centre, edge, and close to the umbilical cord, then cultured under 1% or 6% O2 concentration for 96h. High performance liquid chromatography-mass spectrometry (HPLC-MS)was used to determine the presence and changes of metabolic products in conditioned culture medium with placental villous explants. Results;There were no discernable differences of metabolic footprint among samples taken from the edge, centre or close to umbilical cord in one placenta at 1 % or 6% oxygen tension(P>0. 05). 545 metabolite products in normal pregnancy showed statistically significant differences between 1% or 6% O2(P<0. 05). Principal components analysis (PCA) demonstrated that there were no differences between 1% O2 or 6% O2 in severe preeclampsia, and there were no differences between normal pregnancy under 1% O2 and severe preeclampsia under 6% O2. Conclusions: Hypoxia may have an effect on the metabolic changes of placental villous and may have a role in the pathogenesis of severe preeclampsia. HPLC-MS can be used to identify metabolic differences in placental explants of normal pregnancyor severe preeclampsia under different oxygen tension, thus can be used in the study of the pathogenesis ofsevere preeclampsia.