本课题组研究发现，给予外源性干预促进血管新生，能减轻脑出血小鼠神经功能损伤，但脑出血后血管新生的内源性机制不清。长链非编码RNA（LncRNA）MALAT1在血管内皮中高表达，其水平升高，可促进血管新生；微小RNA（miR）-451可通过阻断其下游IL-6R/STAT3信号通路，抑制血管新生。本项目拟采用脑微血管内皮细胞和miR-451基因敲除小鼠构建脑出血的体外细胞模型和动物模型，上调或下调MALAT1水平，观察miR-451/IL-6R/STAT3信号通路中各因子水平变化，观察血管内皮细胞的细胞周期、迁徙和成管能力的变化，显微光学切片断层成像系统（MOST，Science 2010）显示全脑微血管，并量化分析。从多水平验证MALAT1/miR-451/IL-6R/STAT3通路是脑出血后调控血管新生的重要机制，MALAT1是调控机制中的关键因子，为靶向RNA的小分子药物研发寻找新靶点。

Our previous study has shown that EGb761, an extract of Ginkgo biloba, administration reduces neuronal apoptosis and promotes angiogenesis in experimental intracerebral hemorrhage (ICH) mice. While the endogenous mechanisms of angiogenesis in ICH are still unclear. Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) is an endothelial-enriched long noncoding RNA (lncRNA), which has an interesting function to sustain endothelial cell proliferation. MALAT1 upregulation promotes angiogenesis in some physiologic and pathologic conditions. microRNA(miR)‑451 acts as a suppressor for angiogenesis by targeting IL-6R/STAT3 signaling pathway. In this project, we will establish an in vitro model mimicing ICH in primary brain microvascular endothelial cells (BMECs) and an in vivo model of ICH in miR451 knockout mice. Up-regulate or down-regulate MALAT1 and the mRNA transcription or protein expression of miR-451/IL-6R/STAT3 signaling pathway will be measured. The changes about cell cycle, migration and tube formation of BMECs will be detected. We will use modified Nissl staining combined with micro-optical sectioning tomography (MOST, Science 2010) to directly visualize and evaluate the vascular networks in whole brain. In a word, the molecular mechanisms of MALAT1 promoting angiogenesis in experimental ICH via miR-451/IL-6R/STAT3 signaling pathway will be explored from multiple perspectives. MALAT1 may be a potential target of RNA-targeted small molecules drugs for ICH.