目的 探讨基质细胞衍生因子⁃1α/趋化因子 CXC 受体 4（SDF⁃1α/CXCR4）诱导内皮祖细胞 （EPCs）血管新生在脑卒中神经康复中的作用。方法 采用流式细胞仪和 ELISA 法分析 EPCs 对氧糖剥 夺（OGD）诱导人脑微血管内皮细胞（HBMECs）凋亡、SDF⁃1α 水平的影响。大鼠建立大脑中动脉闭塞 （MCAO）模型，分别采用 EPCs、缺氧内皮细胞条件培养液预处理 EPCs（HBMECs⁃pEPCs）或 AMD3100 （CXCR4拮抗剂）进行治疗。在第6周时通过Morris 水迷宫试验评估大鼠认知功能，和第7周时采用免疫荧 光染色观察大脑皮层血管生成情况。结果 EPCs 处理降低 OGD 诱导的 HBMECs 凋亡率（P < 0.05），并增加血管环数（P < 0.05）。OGD⁃HBMECs 诱导 EPCs 中 SDF⁃1α 表达增加（P < 0.05）。CXCR4 基因敲除减轻了 EPCs 对 OGD⁃HBMECs 的抗凋亡作用（P < 0.05）。MCAO 大鼠在建模后第 4 天时大脑皮层中 EPCs、Claudin5 阳性血管数量和 SDF⁃1α 蛋白水平明显增加（P < 0.05）。与 EPCs 治疗相比，HBMECs⁃pEPCs 治疗能显著增 加大鼠 MCAO 模型的血管密度（P < 0.05），并改善学习记忆障碍，而 AMD3100 逆转了 HBMECs⁃pEPCs 的治 疗作用。结论 HBMECs⁃pEPCs 通过 SDF⁃1α/CXCR4 轴有效地促进大鼠 MCAO 模型神经血管重塑和认知 功能恢复。

Objective To investigate the role of vascular endothelial progenitor cells（EPCs）angiogenesis induced by SDF⁃1α/CXCR4 in neurological rehabilitation after stroke. Methods Flow cytometry and ELISA were used to analyze the effects of EPCs on oxygen⁃glucose deprivation（OGD）⁃induced apoptosis and SDF⁃1α levels in human brain microvascular endothelial cells（HBMECs）. A rat model of MCAO was established. EPCs were pretreat⁃ ed with EPCs，HBMECs⁃pEPCs or AMD3100（CXCR4 antagonist），respectively. Cognitive function was assessed by Morris water maze test at week 6，and angiogenesis in cerebral cortex was observed by immunofluorescence staining at week 7. Results EPCs treatment decreased the apoptotic rate of HBMECs induced by OGD（P < 0.05） and increased the number of vascular ring（P < 0.05）. OGD⁃HBMECs induced an increase in SDF⁃1α expression in EPCs，and CXCR4 knockdown alleviated the anti⁃apoptosis effect of EPCs on OGD⁃HBMECs（P < 0.05）. The number of EPCs and vessels with positive Claudin5 and level of SDF⁃1α protein in cerebral cortex of MCAO rats markedly increased on day 4 after the model establishment（P < 0.05）. As compared with EPCs treatment，HBMECs⁃pEPCs treatment significantly increased vascular density（P < 0.05）and improved deficits of learning and memory in the rat model of MCAO，while AMD3100 reversed the therapeutic effect of HBMECs⁃pEPCs. Conclusions HBMECs⁃ pEPCs can effectively promote neurovascular remodeling and cognitive function recovery via SDF⁃1α⁃CXCR4 axis in the rat model of MCAO.