HSPB8 overexpression prevents disruption of blood-brain barrier after intracerebral hemorrhage in rats through Akt/GSK3β/β-catenin signaling pathway.
HSPB8 overexpression prevents disruption of blood-brain barrier after intracerebral hemorrhage in rats through Akt/GSK3β/β-catenin signaling pathway.
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HSPB8 过表达通过 Akt/GSK3 预防大鼠脑出血后血脑屏障的破坏
DOI：
10.18632/aging.103773
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发表时间：
2020-09-04
期刊：
影响因子：
--
通讯作者：
Yang B
中科院分区：
文献类型：
--
作者：
Hou Y;Hu Z;Gong X;Yang B
血脑屏障（bloodbrain barrier，BBB）破坏是脑出血（intracerebral hemorrhage，ICH）后继发性脑损伤的重要因素。热休克蛋白B8（HSPB 8）通过维持血脑屏障的完整性对缺血性脑卒中具有神经保护作用。然而，HSPB 8在ICH中的作用仍然是难以捉摸的。在本研究中，我们发现HSPB 8在脑出血后上调，并广泛表达于神经血管结构，包括内皮细胞和星形胶质细胞。脑室内（i.c.v）注射慢病毒可在脑组织中实现广泛和持续的HSPB 8过表达。HSPB 8过表达可显著改善脑出血后24和72 h的神经行为障碍和脑水肿。HSPB 8过表达可显著抑制脑出血后24 h血脑屏障的破坏，并显著增加p-Akt、p-GSKβ和核内β-catenin的水平。Akt特异性抑制剂MK2206可明显逆转这种作用。HSPB 8可能通过Akt/ p-GSKβ/β-catenin通路发挥其对血脑屏障的保护作用。
Blood brain barrier (BBB) disruption is a crucial factor contributing to secondary brain injury after intracerebral hemorrhage (ICH). Heat shock protein B8 (HSPB8) has been recently reported to confer neuroprotection against against ischaemic stroke through maintaining BBB integrity. However, the role of HSPB8 in ICH is still elusive. In this study, we found that HSPB8 was upregulated by ICH and extensively expressed in neurovascular structure including endothelial cells and astrocytes. lentivirus intracerebroventricular (i.c.v) injection achieved a widespread and persistent HSPB8 overexpression in brain tissues. HSPB8 overexpression significantly ameliorated neurobehavioral deficits and brain edema at 24 and 72h following ICH. Moreover, HSPB8 overexpression remarkedly inhibited BBB disruption and significantly increase the level of p-Akt, p-GSKβ and intranuclear β-catenin 24h post-ICH. This effect was obviously reversed by Akt specific inhibitor, MK2206. Based on these findings, HSPB8 exerted its protective effect on BBB, at least partly, via Akt/ p-GSKβ/β-catenin pathways.
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