脑卒中后切应力变化介导血管内皮eNO/PGs失衡损害脑血流自动调节

我们已经证明了缺血性脑卒中急性期脑血流自动调节能力（CA）下降加重病情，体外反博通过增加脑血流速度改善脑卒中预后。然而，脑卒中后CA下降的确切机制尚不清楚。脑卒中伴随局部血流动力学障碍和切应力降低。血流切应力通过内皮型一氧化氮（eNO）/cGMP正性及前列腺素（PGs）/TP受体负性调控系统共同调节内皮功能，其降低引起内皮功能障碍。已有的研究显示，CA受内皮功能调控。由此，我们提出脑卒中后CA下降并致病情进展的新机制，即卒中后血流切应力降低抑制内皮依赖性血管舒张功能，使血流自动调节下限上移，降低半暗带脑组织灌注量。本项目拟进一步采用临床试验、动物模型及血管体外应力系统等方法，旨在获得脑卒中后切应力变化介导内皮eNO/PGs失衡损害CA的可靠证据。本项目将阐明脑卒中后血流切应力减小对促卒中进展的CA下降的调控作用和机制，为确立切应力干预作为脑卒中治疗新靶点提供更充分的科学依据。

We demonstrated impaired cerebral autoregulation (CA) may lead to severe stroke and external counterpulsation can improve the prognosis of stroke patients by increasing cerebral blood flow. However, the exact mechanism that CA change in stroke is still unclear. Ischemic stroke leads to regional decreased blood flow perfusion and low vascular shear stress. Shear stress, acting through endothelial nitric oxide (eNO) / cGMP positive and prostaglandins (PGs) / TP receptor negative regulation system, regulates endothelial function. Decreased shear stress in stroke patients may cause endothelial dysfunction. Previous studies show that CA is regulated by endothelial function. Thus, we propose a new mechanism of how CA dysfunction effecting on stroke progression: lower shear stress inhibits endothelium-dependent vasodilation and up-regulates CA lower limit, which may reduce brain blood flow perfusion, especially within penumbra area. The proposed project intends to prove the above mechanism by performing experiments in clinical trial, animal experiment and blood vessels vitro stress system. We aim to demonstrate that lower blood flow perfusion and lower shear stress after ischemic stroke could impair CA by mediating the vascular endothelial eNO / PGs imbalance. This project will elucidate the role and mechanism of decreased post-stroke shear stress in regulation of CA, to provide more adequate scientific basis to establish shear stress intervention and endothelial function as a new target for stroke treatment.