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沉默调节蛋白1介导大鼠高压氧预处理后局灶性脑缺血所致认知缺陷的改善。

Sirt1 mediates improvement in cognitive defects induced by focal cerebral ischemia following hyperbaric oxygen preconditioning in rats.

作者信息

Ding P, Ren D, He S, He M, Zhang G, Chen Y, Sang H, Peng Z, Yan W

机构信息

Department of Anesthesiology, Gansu Provincial Hospital, Lanzhou, China, Department of Psychiatry, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi, China. pengzhengwu1446@ 163.com and

出版信息

Physiol Res. 2017 Dec 20;66(6):1029-1039. doi: 10.33549/physiolres.933544. Epub 2017 Sep 22.

DOI:10.33549/physiolres.933544
PMID:28937253
Abstract

Hyperbaric oxygen preconditioning (HBO-PC) has been proposed as a safe and practical approach for neuroprotection in ischemic stroke. However, it is not known whether HPO-PC can improve cognitive deficits induced by cerebral ischemia, and the mechanistic basis for any beneficial effects remains unclear. We addressed this in the present study using rats subjected to middle cerebral artery occlusion (MCAO) as an ischemic stroke model following HBO-PC. Cognitive function and expression of phosphorylated neurofilament heavy polypeptide (pNF-H) and doublecortin (DCX) in the hippocampus were evaluated 14 days after reperfusion and after short interfering RNA-mediated knockdown of sirtuin1 (Sirt1). HBO-PC increased pNF-H and DCX expression and mitigated cognitive deficits in MCAO rats. However, these effects were abolished by Sirt1 knockdown. Our results suggest that HBO-PC can protect the brain from injury caused by ischemia-reperfusion and that Sirt1 is a potential molecular target for therapeutic approaches designed to minimize cognitive deficits caused by cerebral ischemia.

摘要

高压氧预处理(HBO-PC)已被提议作为缺血性中风神经保护的一种安全实用方法。然而,尚不清楚HPO-PC是否能改善脑缺血诱导的认知缺陷,且任何有益作用的机制基础仍不明确。在本研究中,我们以大脑中动脉闭塞(MCAO)大鼠作为缺血性中风模型,在HBO-PC后对其进行研究。在再灌注14天后以及经短发夹RNA介导敲低沉默调节蛋白1(Sirt1)后,评估海马体中磷酸化神经丝重链多肽(pNF-H)和双皮质素(DCX)的认知功能及表达。HBO-PC增加了MCAO大鼠pNF-H和DCX的表达,并减轻了认知缺陷。然而,这些作用在Sirt1敲低后被消除。我们的结果表明,HBO-PC可保护大脑免受缺血再灌注损伤,且Sirt1是旨在最小化脑缺血所致认知缺陷的治疗方法的潜在分子靶点。

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