脑出血是一种高发病率、高致残率和高死亡率的全球性疾病，目前其治疗尚无突破性进展。课题组前期研究表明骨髓间充质干细胞（BM-MSCs）移植有助于大鼠脑出血后血脑屏障及神经损伤的修复。既往研究表明miR-126促进血管新生和血管完整性，调控PI3K/Akt通路抑制血管内皮细胞凋亡，miR-128能够靶向Wnt3a抑制干细胞向神经细胞分化，因此我们推测miR-126过表达/miR-128沉默能促进BM-MSCs向血管内皮细胞和神经细胞分化，增强BM-MSCs的修复作用。本研究拟构建miR-126过表达/miR-128沉默的BM-MSCs，观察基因修饰对BM-MSCs增殖、凋亡、分化、归巢及抗炎能力的影响，并在脑出血大鼠模型中验证miR-126/miR-128修饰的BM-MSCs对血脑屏障及神经损伤的修复作用，并通过检测相关信号通路进一步明确其作用的分子机制，为脑出血的防治提供新的理论基础。

Intracerebral hemorrhage (ICH) is global disease with high morbidity, mortality and disability rate, and there is still no breakthrough in the treatment for ICH. Our previous research indicated that bone marrow mesenchymal stem cells (BM-MSCs) ameliorate blood-brain barrier dysfunction and neurological deficits after ICH in spontaneously hypertensive rats. Evidence suggests that miR-126 promotes angiogenesis and vascular integrity, and inhibits apoptosis in vascular endothelial cells through PI3K/Akt signal pathway. miR-128 decreased the neural differentiation of BM-MSCs by binding to a specific site in the 3'UTR of Wnt3a. Accordingly we speculate that overexpressing miR-126 or silencing miR-128 enhances the reparing effect of BM-MSCs by promoting BM-MSCs differentiation into vascular endothelial cells and neurons. In this research, miR-126 overexpressed or miR-128 silenced BM-MSCs will be constructed, and the effect of genetic modification on cell proliferation, apoptosis, differentiation, homing ability and anti-inflammatory properties will be analyzed. The effect of miR-126 and miR-128 on BM-MSCs repairing blood-brain barrier and nerve damage after ICH will be verified in the rat model of ICH, and the related signal pathways will be examined to clarify the molecular mechanism. The intended results will provide new theoretical base for ICH therpy.