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The destructive role of soluble Robo4 secreted by the M1-polarized-microglia during cerebral ischemia-reperfusion in blood-brain barrier integrity
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- Author:
- No author available
- Journal Title:
- Acta Physiologica Sinica
- Issue:
- 4
- DOI:
- 10.13294/j.aps.2022.0052
- Key Word:
- 脑缺血再灌注;血脑屏障;脑小胶质细胞;M1极化;sRobo4
Abstract： 本文旨在研究缺血再灌注过程中小胶质细胞的极化对血脑屏障的调控作用和机制.构建脑缺血再灌注的小鼠模型后,小鼠外周血中IL-6、TNF-α表达明显升高,脑组织中IL-6和iNOS mRNA表达增加,iNOS的蛋白表达水平增加,小胶质细胞呈现出明显的M1极化趋势.在体外对脑小胶质细胞Bv-2进行糖氧剥夺后复氧复糖(oxygen-glucose deprivation/reoxygen-ation,OGD/R)处理,在细胞培养上清中检测到TNF-α、IL-6表达明显上升,细胞内IL-6、iNOS和CD86 mRNA表达增加,IL-6和iNOS蛋白表达增加.RNAseq检测结果显示,诱导M1极化的Bv-2细胞和OGD/R处理的Bv-2细胞中Robo4(roundabout guidance receptor 4)的表达都显著增加.进一步研究发现M1极化的Bv-2细胞和OGD/R处理的Bv-2细胞外泌可溶性Robo4蛋白(soluble roundabout guidance receptor 4,sRobo4)也显著增加,并且Robo4重组蛋白、M1极化Bv-2细胞培养上清或OGD/R处理的Bv-2细胞培养上清都能够使内皮细胞的紧密结构破坏.此外,Robo4在急性脑大血管闭塞取栓术后再灌注的患者血清中也有高表达.上述结果显示,脑缺血再灌注过程中M1极化的小胶质细胞分泌Robo4增加可能是引起血脑屏障损伤的原因之一,Robo4有可能作为血脑屏障功能保护的治疗靶点之一.
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