Protocatechuic acid attenuates brain edema and blood-brain barrier disruption after intracerebral hemorrhage in mice by promoting Nrf2/HO-1 pathway
Protocatechuic acid attenuates brain edema and blood-brain barrier disruption after intracerebral hemorrhage in mice by promoting Nrf2/HO-1 pathway
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原儿茶酸通过促进Nrf2/HO-1通路减轻小鼠脑出血后脑水肿和血脑屏障破坏
DOI：
10.1097/wnr.0000000000001542
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发表时间：
2020-11
期刊：
影响因子：
1.7
通讯作者：
Zhiyu Xi;Xiao Chen;Can-xin Xu;Bao-feng Wang;Zhi-hong Zhong;Qingfang Sun;Yuhao Sun;L. Bian
中科院分区：
文献类型：
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作者：
Zhiyu Xi;Xiao Chen;Can-xin Xu;Bao-feng Wang;Zhi-hong Zhong;Qingfang Sun;Yuhao Sun;L. Bian
脑出血后的脑水肿在脑出血后的恢复过程中起着关键作用。原儿茶酸（PCA）对脑出血具有神经保护作用。本文旨在探讨其在脑出血后脑水肿中的作用及其机制。使用胶原酶IV在C57小鼠中创建ICH模型。PCA组腹腔注射PCA 30 mg/kg，每24 h 1次。脑出血后第3天，PCA组出血侧大脑半球含水量较溶剂组显著降低。PCA组主要水通道AQP 4明显减少。PCA组ZO-1和occludin表达增加。培养bEnd.3细胞以了解PCA对血脑屏障（BBB）完整性的影响。与氯化血红素组相比，PCA+氯化血红素组HO-1和Nrf 2核转位表达增强。PCA治疗组HO-1、ZO-1、occludin的过表达在Nrf 2基因敲低后受到抑制。以上结果表明PCA通过促进Nrf 2/HO-1信号通路，减轻脑出血后脑水肿和血脑屏障破坏。
The brain edema following intracerebral hemorrhage (ICH) plays a key role in the recovery process. Protocatechuic acid (PCA) has been proved possessing neuroprotection in ICH. Here we tried to explore its value in brain edema after ICH and reveal underlying mechanisms. ICH model was created in C57 mice using collagenase IV. PCA was injected intraperitoneally at 30 mg/kg every 24 h in PCA group. On day 3 after ICH, the water content of hemorrhagic ipsilateral hemisphere in PCA group was significantly reduced compared with vehicle group. AQP4, the main water channel, was remarkably decreased in PCA group. Additionally, ZO-1 and occludin expression were increased in PCA group. The bEnd.3 cells were cultured to understand the effect of PCA on the blood-brain barrier (BBB) integrity. Compare to hemin treated group, plus PCA enhanced the expression of HO-1 and Nrf2 nuclear translocation. Furtherly, the overexpression of HO-1, ZO-1, occludin, in the PCA treatment group was inhibited after knockdown of Nrf2. Taken together, our results proved PCA alleviated brain edema and BBB disruption in ICH by promoting the Nrf2/HO-1 signaling pathway.