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预先给予比索洛尔和维生素 E 单独或联合治疗可提供针对大鼠脑缺血/再灌注损伤的神经保护作用。

Pretreatment with bisoprolol and vitamin E alone or in combination provides neuroprotection against cerebral ischemia/reperfusion injury in rats.

机构信息

Department of Pharmacology and Toxicology, School of Pharmacy, Urmia University of Medical Sciences, PO Box 5715799313, Urmia, Iran.

出版信息

Naunyn Schmiedebergs Arch Pharmacol. 2021 Apr;394(4):685-695. doi: 10.1007/s00210-020-02007-9. Epub 2020 Oct 27.

Abstract

Global cerebral ischemia/reperfusion (I/R) induces selective neuronal injury in the hippocampus, leading to severe impairment in behavior, learning, and memory functions. This study aimed to evaluate the neuroprotective effects of bisoprolol (biso) and vitamin E (vit E) treatment alone or in combination on cerebral ischemia/reperfusion (I/R) injury. A total of 30 male rats were divided randomly into five groups (n = 6), sham, I/R, I/R + biso, I/R + vit E, and I/R + biso+vit E. Cerebral I/R group underwent global ischemia by bilateral common carotid artery occlusion for 20 min. Treatment groups received drugs once daily intraperitoneally for 7 days before the I/R induction. Locomotive and cognitive behaviors were utilized by open-field and Morris water maze tests. After behavioral testing, the brain was removed and processed to evaluate cerebral infarct size, histopathologic changes, myeloperoxidase (MPO) activity, and malondialdehyde (MDA) level. In I/R group tissue MDA and MPO levels and cerebral infarct size were significantly increased in comparison with the sham group. Furthermore, significant deficits were observed in locomotion and spatial memory after I/R. The areas of cerebral infarction, MPO, and MDA levels in biso, vit E, and combination group were significantly reduced compared with I/R group. Histopathological analysis demonstrated a significant reduction in leukocyte infiltration in all treated groups with the most profound reduction in the combination group. According to the behavioral tests, administration of biso and/or vit E protected locomotive ability and improved spatial memory after cerebral I/R. Our findings show that biso and vit E have beneficial effects against the I/R injury and due to their synergistic effects when administered in combination, may have a more pronounced protective effect on the cerebral I/R injury.

摘要

全球脑缺血/再灌注(I/R)诱导海马选择性神经元损伤,导致严重的行为、学习和记忆功能障碍。本研究旨在评估比索洛尔(biso)和维生素 E(vit E)单独或联合治疗对脑缺血/再灌注(I/R)损伤的神经保护作用。总共 30 只雄性大鼠随机分为 5 组(n = 6),假手术、I/R、I/R + biso、I/R + vit E 和 I/R + biso+vit E。I/R 组通过双侧颈总动脉闭塞缺血 20 分钟。治疗组在 I/R 诱导前每天腹腔注射药物一次,共 7 天。使用旷场和 Morris 水迷宫测试评估运动和认知行为。行为测试后,取出大脑并处理以评估脑梗死面积、组织病理学变化、髓过氧化物酶(MPO)活性和丙二醛(MDA)水平。与假手术组相比,I/R 组组织 MDA 和 MPO 水平以及脑梗死面积明显增加。此外,I/R 后观察到运动和空间记忆明显缺陷。与 I/R 组相比,biso、vit E 和联合组的脑梗死面积、MPO 和 MDA 水平均显著降低。组织病理学分析表明,所有治疗组的白细胞浸润均明显减少,联合组减少最明显。根据行为测试,biso 和/或 vit E 给药可保护运动能力,并改善脑 I/R 后的空间记忆。我们的研究结果表明,biso 和 vit E 对 I/R 损伤具有有益作用,并且由于它们联合给药时的协同作用,可能对脑 I/R 损伤具有更明显的保护作用。

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