Heat shock proteins (HSPs) may be induced by hypoxia and alleviate blood-brain barrier (BBB) damage. The neuroprotective effect of propofol has been reported. We aimed to identify whether propofol induced HSPs expression and protected BBB integrity. Mouse astrocytes and microglia cells were cultured and exposed to hypoxia and propofol. The expression of HSP27, HSP32, HSP70, and HSP90, and the translocation of heat shock factor 1 (HSF1) and Nuclear factor-E2-related factor 2 (Nrf2) were investigated. Mouse brain microvascular endothelial cells, astrocytes, and microglial cells were co-cultured to establish in vitro BBB model, and the effects of hypoxia and propofol as well as HSPs knockdown/overexpression on BBB integrity were measured. Hypoxia (5% O2, 5% CO2, 90% humidity) treatment for 6 h and 12 h induced HSP27, HSP32, and HSP70 expression. Propofol (25 μΜ) increased HSP27 and HSP32 expression, starting with exposure to hypoxia for 3 h. Propofol induced HSF1 translocation from cytoplasmic to nuclear compartment, and blockade of HSF1 inhibited HSP27 expression in mouse astrocytes when they were exposed to hypoxia for 3 h. Propofol induced Nrf2 translocation, and blockade of Nrf2 inhibited HSP32 expression in mouse microglial cells when they were exposed to hypoxia for 3 h. Propofol protected hypoxia-impaired BBB integrity, and the effects were abolished by blockade of HSF1 and Nrf2. Overexpression of HSP27 and HSP32 alleviated hypoxia-impaired BBB integrity, and blockade of HSP27 and HSP32 expression ameliorated propofol-mediated protection against BBB impairment. Propofol may protect hypoxia-mediated BBB impairment. The mechanisms may involve HSF1-mediated HSP27 expression and Nrf2-mediated HSP32 expression.

中文翻译：

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丙泊酚对缺氧调节热休克蛋白表达的影响：调节血脑屏障通透性的潜在机制。

缺氧可诱导热休克蛋白 (HSP) 并减轻血脑屏障 (BBB) 损伤。异丙酚的神经保护作用已有报道。我们旨在确定异丙酚是否诱导 HSP 表达并保护 BBB 完整性。小鼠星形胶质细胞和小胶质细胞被培养并暴露于缺氧和丙泊酚。研究了 HSP27、HSP32、HSP70 和 HSP90 的表达，以及热激因子 1 (HSF1) 和核因子-E2 相关因子 2 (Nrf2) 的易位。共培养小鼠脑微血管内皮细胞、星形胶质细胞和小胶质细胞建立体外血脑屏障模型，并测定缺氧和丙泊酚以及HSPs敲低/过表达对血脑屏障完整性的影响。缺氧（5% O2、5% CO2、90% 湿度）处理 6 小时和 12 小时可诱导 HSP27、HSP32 和 HSP70 表达。丙泊酚 (25 μM) 增加 HSP27 和 HSP32 的表达，从暴露于缺氧 3 小时开始。丙泊酚诱导 HSF1 从细胞质转移到核区室，当小鼠星形胶质细胞暴露于低氧 3 小时时，阻断 HSF1 可抑制 HSP27 的表达。丙泊酚诱导 Nrf2 易位，当小鼠小胶质细胞暴露于低氧 3 小时时，阻断 Nrf2 可抑制 HSP32 的表达。异丙酚保护缺氧损害的 BBB 完整性，并且通过阻断 HSF1 和 Nrf2 消除了这种影响。HSP27 和 HSP32 的过表达减轻了缺氧损害的 BBB 完整性，阻断 HSP27 和 HSP32 表达改善了丙泊酚介导的对 BBB 损害的保护。异丙酚可以保护缺氧介导的 BBB 损伤。