Vitamin D prevents hypoxia/reoxygenation-induced blood-brain barrier disruption via vitamin D receptor-mediated NF-kB signaling pathways.
Vitamin D prevents hypoxia/reoxygenation-induced blood-brain barrier disruption via vitamin D receptor-mediated NF-kB signaling pathways.
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DOI：
10.1371/journal.pone.0122821
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Stein DG
中科院分区：
文献类型：
--
作者：
Won S;Sayeed I;Peterson BL;Wali B;Kahn JS;Stein DG
维持血脑屏障完整性和最大限度地减少神经元损伤是缺血性卒中后任何治疗干预的关键组成部分。然而，低水平的维生素D激素是许多血管疾病包括中风的危险因素。已经研究了1，25（OH）2D 3（维生素D）在缺血性中风后的神经保护作用，但尚不清楚它是否能预防脑内皮细胞（神经血管单元的关键组成部分）的缺血性损伤。我们在小鼠脑内皮细胞培养模型中分析了缺氧/复氧后1，25（OH）2D 3对脑内皮细胞屏障完整性和紧密连接蛋白的影响，该模型密切模拟了体外血脑屏障的许多特征。在bEnd.3细胞中缺氧损伤后，1，25（OH）2D 3处理防止了屏障功能的降低，如通过跨内皮电阻和FITC-葡聚糖（40 kDa）的渗透性所测量的，防止了紧密连接蛋白小带闭合蛋白-1，claudin-5和闭合蛋白表达的降低，防止了NF-kB的活化，以及防止了基质金属蛋白酶-9表达的增加。当5 '-磷酸吡哆醛处理抑制1，25（OH）2D 3与维生素D受体（VDR）的相互作用时，这些反应被阻断。我们的研究结果表明，在脑内皮细胞中，1，25（OH）2D 3对缺血性损伤诱导的血脑屏障功能障碍具有直接的、VDR介导的保护作用。
Maintaining blood-brain barrier integrity and minimizing neuronal injury are critical components of any therapeutic intervention following ischemic stroke. However, a low level of vitamin D hormone is a risk factor for many vascular diseases including stroke. The neuroprotective effects of 1,25(OH)2D3 (vitamin D) after ischemic stroke have been studied, but it is not known whether it prevents ischemic injury to brain endothelial cells, a key component of the neurovascular unit. We analyzed the effect of 1,25(OH)2D3 on brain endothelial cell barrier integrity and tight junction proteins after hypoxia/reoxygenation in a mouse brain endothelial cell culture model that closely mimics many of the features of the blood-brain barrier in vitro. Following hypoxic injury in bEnd.3 cells, 1,25(OH)2D3 treatment prevented the decrease in barrier function as measured by transendothelial electrical resistance and permeability of FITC-dextran (40 kDa), the decrease in the expression of the tight junction proteins zonula occludin-1, claudin-5, and occludin, the activation of NF—kB, and the increase in matrix metalloproteinase-9 expression. These responses were blocked when the interaction of 1,25(OH) )2D3 with the vitamin D receptor (VDR) was inhibited by pyridoxal 5’-phosphate treatment. Our findings show a direct, VDR-mediated, protective effect of 1,25(OH) )2D3 against ischemic injury-induced blood-brain barrier dysfunction in cerebral endothelial cells.
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影响因子：
3.1
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