血管新生是卒中后修复基础，但一些促血管新生分子常可致血管炎症损伤，因此，亟待探索促血管修复新策略。我们和他人研究发现，miR-92a负向调节促血管新生关键分子整合素ɑ5β1和抗炎因子KLF4，提示抑制miR-92a有促血管新生和减轻炎症反应的双重作用潜能。还发现miR-92a受上游lncRNA XIST调控。由此推测，卒中时上调lncRNA XIST可能通过miR-92a-ɑ5β1/KLF4途径达到促血管新生同时对抗炎症损伤。本项目拟采用缺血性脑卒中模型，运用基因调控、共聚焦成像和免疫沉淀等技术，在细胞和动物水平探究抑制miR-92a或上调lncRNA XIST是否有促血管新生和抑制炎症反应的双重作用；确定lncRNA XIST是否藉调控miR-92a-α5β1/KLF4通路达到促卒中后血管新生和对抗血管炎症损伤；并阐明其内在分子机制。该项目将为卒中后血管保护提供新靶标，为治疗提供新思路。

To promote the cerebral angiogenesis and reduce the concomitant severe vascular inflammtory injury after ischemic stroke is a promising target for stroke treatment. Our previous work demonstrated that the α5β1 integrin plays a key role in promoting cerebral angiogenesis in response to cerebral ischemia/reperfusion injury (CI). However, upregulating the integrin α5β1 alone will increase the risk of inflammation after CI. We also found that long noncoding RNA-X inactivate-specific transcript (lncRNA XIST) interacts directly with the microRNA molecule, miR-92a. And the latter negatively regulate cerebral collateral circulation of CI patients and the expression of α5β1 on brain endothelial cells (BECs). It is reported that inhibiting the expression of miR-92a promotes the angiogenesis and reduces the leukocyte influx after myocardial infarction as well as attenuates the endothelial inflammation by upregulating the anti-inflammtion factor- Krüppel-like factor 4 (KLF4). Here, we hypothesize that lncRNA XIST promotes angiogenesis and attenuates vascular inflammtory injury through regulating miR-92a-α5β1/KLF4 after CI. In the current study, we will examine the precise relationship between lncRNA XIST, miR-92a and integrin α5β1/ KLF4, and observe the regulating effect of lncRNA XIST by targeting miR-92a-α5β1/ KLF4 axis to promote the angiogenesis and inhibit the inflammation under cerebral ischemic condition vivo and in vitro. Meanwhile, we also evaluate whether α5β1-ERK/Akt and KLF4-nuclear factor-κB signal pathway is involved in these processes after CI. We first propose that lncRNA XIST interacts with miR-92a-α5β1/KLF4 to regulate the cerebral angiogenesis and vascular inflammation after CI by changing the local microenvironment, which provides a more reasonable therapeutic strategy for ischemic stroke recovery.