实用医学杂志 ›› 2022, Vol. 38 ›› Issue (19): 2407-2413.doi: 10.3969/j.issn.1006⁃5725.2022.19.006

• 基础研究 • 上一篇    下一篇

基质细胞衍生因子⁃1α/趋化因子CXC 受体4诱导内皮祖细胞血管新生促进脑卒中的神经康复机制

郭丹1 张娟1 王洪涛1 刘行高1 郭远瑾2   

  1. 1 华中科技大学协和东西湖医院(武汉市东西湖区人民医院)康复医学科(武汉430040); 2 华中科技大学同济医学院附属协和医院神经内科(武汉 430022

  • 出版日期:2022-10-10 发布日期:2022-10-10
  • 基金资助:
    湖北省卫生健康委员会课题(编号:WJ2019F157)

SDF⁃1α/CXCR4 induces endothelial progenitor cell angiogenesis to promote neural rehabilitation following stroke

GUO Dan*,ZHANG Juan,WANG Hongtao,LIU Xinggao,GUO Yuanjin.    

  1. Department of Rehabilitation MedicineUnion Dongxihu Hospital of Huazhong University of Science and TechnologyDongxihu District People′s Hospital of Wuhan),Wuhan 430040China

  • Online:2022-10-10 Published:2022-10-10

摘要:

目的 探讨基质细胞衍生因子⁃1α/趋化因子 CXC 受体 4SDF⁃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 EPCsHBMECs⁃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 SDF⁃1α 表达增加(P < 0.05)。CXCR4 基因敲除减轻了 EPCs 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 EPCsClaudin5 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。

关键词: 内皮祖细胞,  , 人脑微血管内皮细胞,  , 大脑中动脉闭塞,  , 神经血管,  , 基质细胞衍生 , 因子?1α, 趋化因子CXC , 受体4

Abstract:

Objective To investigate the role of vascular endothelial progenitor cellsEPCsangiogenesis 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 deprivationOGD⁃induced apoptosis and SDF⁃1α levels in human brain microvascular endothelial cellsHBMECs. A rat model of MCAO was established. EPCs were pretreat⁃ ed with EPCsHBMECs⁃pEPCs or AMD3100CXCR4 antagonist),respectively. Cognitive function was assessed by Morris water maze test at week 6and angiogenesis in cerebral cortex was observed by immunofluorescence staining at week 7. Results EPCs treatment decreased the apoptotic rate of HBMECs induced by OGDP < 0.05and increased the number of vascular ringP < 0.05. OGD⁃HBMECs induced an increase in SDF⁃1α expression in EPCsand CXCR4 knockdown alleviated the anti⁃apoptosis effect of EPCs on OGD⁃HBMECsP < 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 establishmentP < 0.05. As compared with EPCs treatmentHBMECs⁃pEPCs treatment significantly increased vascular densityP < 0.05and improved deficits of learning and memory in the rat model of MCAOwhile 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.

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