PGF2a通过TP和EP3受体诱发血管收缩和升压反应。我们最新结果提示，PGF2a的原受体FP受体介导一非NO依赖性血管舒张作用。我们结果还显示，PGF2a选择性地在兔脑动脉内皮大量产生，且FP受体在该血管高表达，然而PGF2a却在此诱发较弱的收缩作用。由于PGF2a在糖尿病状态下合成增加及血管疾病时舒张性前列腺素受体常发生表达下调，我们推测：FP受体的高表达导致了PGF2a在脑动脉的较弱收缩作用，但在糖尿病状况下，内皮PGF2a合成增加和FP受体表达降低可导致脑动脉内皮依赖性血管收缩增强、成为脑动脉内皮功能失调的重要原因。本项目将通过基因敲除小鼠、家兔和人体血管结合糖尿病模型对上述假说和科学问题进行验证。预期我们结果将为明确PGF2a的血管调节机制、内皮PGF2a合成对脑动脉的调节及糖尿病脑血管内皮功能失调的病理生理机制提供新的理论和实验依据，从而为该病防治提供新的优化思路或干预信息。

PGF2a evokes strong vasoconstriction and elevates blood pressure through TP and EP3 receptors. Our latest results suggest that the original receptor of PGF2a, the FP receptor mediates a NO-independent vascular dilator effect. Our results also reveal that PGF2a is selectively produced in large amounts by the endothelium of rabbit cerebral artery, but it induces only a weak contractile effect, although the FP receptor is highly expressed in the vessel. Because the synthesis of PGF2a can be increased in diabetes and expressions of dilator prostaglandin receptors can be reduced in vascular diseases, we propose that the high expression of FP receptor is responsible for the weak contractile effect of PGF2a on cerebral arteries, but in diabetic conditions, the increase of endothelial PGF2a synthesis together with a down-regulation of the FP receptor can give rise to increased endothelium-dependent contraction or endothelial dysfunction in cerebral arteries. This project will use gene knockout mice, rabbit and human blood vessels, in combination with the use of diabetes models to verify our above hypotheses. It is expected that the results of our study will provide novel insights on the mechanisms of PGF2a in regulating vascular function, especially that of the regulation of cerebral arteries by endothelial PGF2a synthesis, and those for the development of diabetic cerebrovascular endothelial dysfunction, and hence may lead to new ideas for optimizing the existing therapeutics or provide novel insights on interventions for prevention or treatment of the disease condition.