胎盘内皮PGI2功能特点与妊娠高血压关联的研究

Mechanisms for pregnant hypertension are complicated, as “endothelial damage” is one of hypothesis proposed. Our recently published data demonstrated that placental vascular endothelium is significantly different from non-placental vessels. Classic nitric oxide (NO) mediated endothelial vasodialation is very limited in the placenta, suggesting its contributions to pregnant hypertension is a question. Besides NO, endothelial PGI2 also plays important roles in vascular dilation. Whether PGI2 in placental vessels acts like its NO different from non-placental vessels, and whether it plays roles in development of pregnant hypertension, are questions that will be investigated in this project. This project will use inhibitors for key enzymes of PGI2 and removing endothelium in study of vascular relaxation in micro-vessels from human and animal placenta, and explore functions of endogenous PGI2 in placental vessels. Exogenous PGI2 will also be used to test placental micro-vessels. Placental vessels from both normal and preeclampsia will be determined for their reaction and sensitivity to PGI2. Molecular experiments will examine PGI2 signaling in placental vessels and its roles in development of pregnant hypertension. In addition, single cell technology will be used to study ion channel activities on vascular smooth muscle cells, and simutanously measuring vascular tension and intracellular calcium flux will be used to determine PGI2-mediated vascular functions and possible changes in micro-vessels in preeclampsia. This study with reasonable design should expect novel and important data, which will increase understanding the relationship between PGI2 and placental circulation as well as development of pregnant hypertension.

妊娠高血压机制复杂，内皮受损是众多假说之一。我们刚发表的研究揭示胎盘微血管内皮与非胎盘血管显著不同，经典一氧化氮（NO）介导内皮功能在胎盘很弱，提示对妊娠高血压贡献有限。血管内皮除了NO，前列腺素I2（PGI2）在血管舒张中起重要作用。胎盘血管PGI2是否如同NO那样与非胎盘血管不同，是否在妊娠高血压中发挥作用，是本项目拟解答重要问题。我们将对人与动物胎盘微血管用PGI2关键酶抑制剂或去内皮下研究舒张功能，探讨胎盘血管内源性PGI2功能。用外源性PGI2研究胎盘微血管舒张。比较正常与子痫胎盘微血管对PGI2反应强度与灵敏度，分子检测胎盘血管PGI2通路在妊娠高血压中可能作用与机制。结合血管平滑肌单细胞通道活性检测及用我们国内首创微血管张力与内钙同步检测，研究子痫胎盘PGI2介导微血管功能及其变异。合理科学设计有理由产生若干新颖和重要的研究成果，解释胎盘微血管PGI2与妊娠高血压关系。

虽然胎盘内皮功能受损是妊娠高血压的发病机制众多假说之一，但其机制尚未明了。本项目着重探讨重要血管舒张因子PGI2在胎盘微血管中的作用以及在妊娠高血压中的可能的贡献。研究发现胎盘微血管内皮PGI2的作用显著区别于非胎盘血管，而且内皮PGI2对胎盘内皮因素相关的妊娠高血压的发病机制的贡献很有限。由此发展的新观点和新理论是对妊娠高血压的发病机制研究的重要贡献，而且该新观点和新理论在本研究领域中已经为国际上关注和报道推荐。.研究目标完成情况良好和顺利。在创新与人才培养和SCI杂志论文发表等方面实际完成情况和成果超出原计划的预想和水平。