脑小血管病是指脑部小动脉、毛细血管、小静脉病变导致的一组临床综合征。慢性缺血是小血管病的重要发病机制，很多人认为它是由小动脉硬化导致的。然而我们前期发现小血管病脑血流下降早于小动脉硬化；而缺血早期，毛细血管周细胞已出现改变。这提示毛细血管周细胞改变可能是小血管病早期缺血的原因。我们发现小血管病大鼠脑、脑微血管段和周细胞COX-2高表达，抑制COX-2可减轻血管紧张素所致的周细胞介导的毛细血管收缩，提示COX-2参与小血管病毛细血管周细胞改变。本项目首先在模型动物脑片上观察疾病早期各时间点毛细血管及小动脉舒缩，评估毛细血管改变是否有特异性。然后利用COX-2敲除的小血管病大鼠模型，研究COX-2对小血管病早期周细胞介导的毛细血管舒缩功能的影响。最后探索COX-2通过何种下游前列腺素及受体调控这一过程，经典收缩调控通路ROCK是否参与其中。本项目有望为进一步阐明小血管病早期缺血机制提供新假说。

Cerebral small vessel diseases refer to a syndrome of clinical, cognitive and neuroimaging thought to arise from disease affecting perforating arterioles, capillaries, and venules and resulting brain damage. Chronical ischemic is an important characteristic. While the reason causing early ischemia in cerebral small vessel diseases is still unknown. We found the decline of cerebral blood flow is earlier to arteriolosclerosis and in this time the change of pericyte in capillary has already been found. COX-2 high expressed in cerebral, microvessel and pericyte, and inhibiting COX-2 can relieve the capillary constriction mediated by pericyte causing by Angiotensin II. In the project, we will examine the change of vasomotor function in capillary and arteriole in different time point. Then study the effect of COX-2 on capillary vasomotor mediated by pericyte in cerebral small vessel diseases. Last, we will explore role of the prostaglandin and its receptor and Rho/ROCK signaling on this process. Though this project, we may illuminate the mechanism of early ischemia in cerebral small vessel diseases.