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硫酸镁对急性缺血性脑卒中大鼠血脑屏障完整性的保护作用及脑水肿的减轻作用。

Magnesium sulfate protects blood-brain barrier integrity and reduces brain edema after acute ischemic stroke in rats.

机构信息

Department of Physiology, Medical School, Ardabil University of Medical Sciences, Ardabil, 56197, Iran.

Physiological Studies Research Center, Medical School, Ardabil University of Medical Sciences, Ardabil, Iran.

出版信息

Metab Brain Dis. 2019 Aug;34(4):1221-1229. doi: 10.1007/s11011-019-00419-y. Epub 2019 Apr 29.

Abstract

Brain edema is a fatal complication of acute ischemic stroke and associated with worse outcomes in patients. This study was designed to evaluate the effects of magnesium sulfate on vasogenic brain edema formation and blood-brain barrier (BBB) disruption caused by ischemia-reperfusion (IR) in a rat model of ischemic stroke. A total of 72 male Sprague-Dawley rats were categorized into the following three primary groups: sham, control ischemic, magnesium-sulfate-treated (300 mg/kg loading dose, followed by an additional 100 mg/kg) ischemic (n = 24 in each group). Transient focal cerebral ischemia was induced by 60-min-long occlusion of the left middle cerebral artery, followed by 24-h-long reperfusion. Sensorimotor deficits, infarct volume, and brain edema were evaluated at the end of the reperfusion period. The BBB permeability was assessed by Evans Blue extravasation technique. Lipid peroxidation levels were assessed by measuring the malondialdehyde content in the brain tissue homogenate, and the activities of the antioxidant enzymes superoxide dismutase, catalase, and glutathione peroxidase were detected according to the technical manual of the assay kits. Induction of cerebral ischemia in the control group produced considerable BBB damage in conjunction with severe brain edema formation. Treatment with magnesium sulfate significantly attenuated brain edema and protected BBB integrity in the ischemic lesioned hemisphere. In addition, magnesium sulfate reduced lipid peroxidation and increased antioxidant protection of brain tissue by upregulating the activities of antioxidant enzymes. Treatment with magnesium sulfate protected BBB integrity against IR-induced damage and reduced vasogenic edema formation partly via antioxidant mechanisms in a rat model of acute ischemic stroke.

摘要

脑水肿是急性缺血性中风的致命并发症,并与患者的预后较差相关。本研究旨在评估硫酸镁对缺血再灌注(IR)引起的大鼠缺血性中风模型中血管源性脑水肿形成和血脑屏障(BBB)破坏的影响。将 72 只雄性 Sprague-Dawley 大鼠分为以下三组:假手术组、对照组缺血组和硫酸镁治疗组(300mg/kg 负荷剂量,随后追加 100mg/kg)(每组 24 只)。通过 60 分钟的左侧大脑中动脉闭塞诱导短暂性局灶性脑缺血,随后进行 24 小时的再灌注。在再灌注期末,评估感觉运动缺陷、梗死体积和脑水肿。通过 Evans Blue 外渗技术评估 BBB 通透性。通过测量脑组织匀浆中的丙二醛含量评估脂质过氧化水平,根据试剂盒的技术手册检测抗氧化酶超氧化物歧化酶、过氧化氢酶和谷胱甘肽过氧化物酶的活性。在对照组中诱导脑缺血会导致严重的 BBB 损伤和脑水肿形成。硫酸镁治疗可显著减轻脑水肿并保护缺血损伤半球的 BBB 完整性。此外,硫酸镁通过上调抗氧化酶的活性减轻了脂质过氧化作用并增强了脑组织的抗氧化保护作用。在急性缺血性中风大鼠模型中,硫酸镁通过抗氧化机制保护 BBB 完整性免受 IR 损伤,并减少血管源性水肿形成。

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