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活化蛋白C对局灶性脑缺血/再灌注期间血脑屏障损伤的神经保护作用

Neuroprotective Effect of Activated Protein C on Blood-Brain Barrier Injury During Focal Cerebral Ischemia/Reperfusion.

作者信息

Wang Jinqiao, Rao Gaofeng, Ma Yifan, Zhang Jingjing, Shen Jingjing, Shi Chaohong

机构信息

Department of Rehabilitation Medicine, The First People's Hospital of Wenling, Wenzhou Medical University, Wenling, China.

Department of Chemical and Biomolecular Engineering, The Ohio State University, Columbus, OH, USA.

出版信息

Dose Response. 2020 May 4;18(2):1559325820917288. doi: 10.1177/1559325820917288. eCollection 2020 Apr-Jun.

Abstract

Although the effect of activated protein C (APC) on neuronal injury and neuroinflammatory responses has been extensively studied, the detailed mechanism underlying APC-protective effect in the blood-brain barrier (BBB) injury during ischemia is still not clear. In this study, the APC effect against neuroinflammatory responses was evaluated in the model of right middle cerebral artery occlusion in male Sprague-Dawley rats with 2 hours of ischemia and 22 hours of reperfusion. The results showed that APC can significantly improve the neurological function scoring and reduce the infarct volume and BBB permeability. Moreover, the expression of protein nuclear factor-kappa B (NF-κB), both in cytoplasm and nuclei, was reduced. The downstream of NF-κB activation, including tumor necrosis factor-α and interleukin-1β secretion, was inhibited. In all, APC exerts a neuroprotective effect in focal cerebral ischemia-reperfusion in rats by inhibiting the activation and nuclear translocation of NF-κB. It may indicate a therapeutic approach for ischemic brain injury.

摘要

尽管活化蛋白C(APC)对神经元损伤和神经炎症反应的作用已得到广泛研究,但在缺血期间血脑屏障(BBB)损伤中APC保护作用的详细机制仍不清楚。在本研究中,在雄性Sprague-Dawley大鼠大脑中动脉右支闭塞模型中,评估了APC对神经炎症反应的作用,该模型有2小时缺血和22小时再灌注。结果表明,APC可显著改善神经功能评分,减少梗死体积和血脑屏障通透性。此外,细胞质和细胞核中蛋白核因子-κB(NF-κB)的表达均降低。NF-κB激活的下游,包括肿瘤坏死因子-α和白细胞介素-1β的分泌,均受到抑制。总之,APC通过抑制NF-κB的激活和核转位,对大鼠局灶性脑缺血再灌注发挥神经保护作用。这可能为缺血性脑损伤指明一种治疗方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3191/7218308/a45c4ef6ca9a/10.1177_1559325820917288-fig1.jpg

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