低氧环境下G9a／Notch通路对子痫前期胎盘血管生成调控及其光声／超声微血管显像检测

Placental angiogenesis imbalance is considered important in the pathogenesis of preeclampsia. G9a-mediated transcription switch activating Notch signaling pathway plays a key role in the regulation of placental vascular maturation. Continuous hypoxia environment increases the risk of preeclampsia. So it is speculated that the persistent hypoxia environment and HIF-1a may affect placental angiogenesis by interfering with the expression of G9a and Notch signaling pathways. Traditional research methods can not directly reflect the state of placental oxygenation and microcirculation blood flow, and can not observe the process of placental angiogenesis especially in the first and second trimester. In this study, new imaging techniques, such as photoacoustic imaging and ultrasound microvascular imaging, can be used to noninvasively assess placental oxygen saturation and hemoglobin concentration, real-time detection of placental blood vessel perfusion, which is expected to become a technical means for continuous and dynamic evaluation of placental angiogenesis and its function in vivo. In this study, the expression of G9a and Notch signaling pathways in pregnant rats under hypoxic environment was studied by real-time fluorescent quantitative PCR and Western blotting, and the relationship between G9a and Notch signaling pathways and placenta photoacoustic/ultrasonography imaging was also studied to demonstrate the regulation of angiogenesis. The results of this study will establish a functional placental imaging platform, help the understanding of the pathogenesis of preeclampsia, and provide experimental basis for the early diagnosis of pre-eclampsia.

胎盘血管生成失衡被认为在子痫前期的发病中起核心作用，G9a介导转录开关激活Notch信号通路在胎盘血管成熟调控中起关键作用。持续低氧环境下子痫前期发病率升高，因此推测持续低氧环境及HIF-1通过干扰G9a及Notch信号通路表达而影响胎盘血管生成。传统研究方法不能直观反映胎盘氧合状态及微循环血流状态，不能对胎盘血管生成过程进行动态观察。本研究应用前期工作建立的新型光声成像及超声微血管显像等影像学技术，可无创评估胎盘血氧饱和度及血红蛋白浓度，实时检测胎盘血管灌注情况，有望成为在体连续动态评估胎盘血管生成及其功能的技术手段。本课题将采用实时荧光定量PCR技术、蛋白印迹法等方法研究低氧环境下孕鼠G9a及Notch信号通路的表达，及其与胎盘光声／超声显像的联系，显示其对于血管生成的调控。本研究成果将建立胎盘功能影像学成像平台，加深对子痫前期发病机制的了解，并有望为子痫前期的早期诊断提供实验依据。

研究团队基于前期工作建立的新型光声成像及平面波成像系统，对在不同氧浓度环境下妊娠的孕鼠胎盘进行观察与对比，经过多参数提取、筛选及优化，对胎盘内血氧饱和度、胎盘血管密度等母体、胎盘血管结构、功能学指标情况进行评估。建立了利用光声/超声多模态成像技术平台评估先兆子痫的标准化流程。实现了实时、无创地评估先兆子痫孕鼠血氧饱和度、胎盘血流灌注及分布及血流动力学等表现，在动物水平上，初步验证了光声/超声多模态成像技术可为人体先兆子痫疾病的预测、诊断、治疗及随访提供便捷有效的评估手段，且具有较好的诊断效能，具备临床转化价值。