Department of Pharmacology and Toxicology, Faculty of Pharmacy, Minia University, El-Minia, Egypt.
Life Sci. 2012 Mar 10;90(11-12):388-95. doi: 10.1016/j.lfs.2011.12.001. Epub 2011 Dec 23.
Oxidative stress-induced cell damage is reported to contribute to the pathogenesis of cerebral ischemia/reperfusion injury. This study investigated the neuroprotective effect of nebivolol against cerebral ischemia/reperfusion insult in rats.
The model adopted was that of surgically-induced forebrain ischemia, performed by means of bilateral common carotid artery occlusion for 1h, followed by reperfusion for 24 h. The effects of 5 and 10 mg/kg nebivolol, treated for 7 days prior to ischemia/reperfusion insult, were investigated by estimating endothelial and inducible nitric oxide synthases (eNOS and iNOS) protein expressions and assessing oxidative stress-related biochemical parameters in the rat forebrain. Also, infarct volume measurement and histopathological study of the forebrain were examined.
Administration of nebivolol increased eNOS expression with simultaneous decrease in iNOS expression in a dose dependent manner. Moreover, nebivolol inhibited ischemia/reperfusion-induced depletion of reduced glutathione level and decreased the elevated total nitric oxide end production and malondialdehyde levels, superoxide dismutase and lactate dehydrogenase activities. A notable finding is that catalase activity was not changed in response to either ischemia/reperfusion insult or nebivolol treatment. However, the results confirmed that nebivolol significantly reduced infarct volume and alleviated ischemia/reperfusion-induced histopathological changes.
The present study demonstrates the neuroprotective effect of nebivolol against cerebral ischemia/reperfusion insult. Neuroprotection observed with nebivolol may possibly be explained by regulating eNOS and iNOS expressions and by inhibition of oxidative stress-induced injury. Thus, nebivolol may be considered as a potential candidate for treatment in patients who are prone to stroke.
氧化应激诱导的细胞损伤被认为有助于脑缺血/再灌注损伤的发病机制。本研究旨在探讨奈必洛尔对大鼠脑缺血/再灌注损伤的神经保护作用。
采用手术诱导的前脑缺血模型，通过双侧颈总动脉闭塞 1 小时，再灌注 24 小时。在缺血/再灌注损伤前 7 天，分别用 5 和 10mg/kg 的奈必洛尔进行治疗，通过估计内皮型和诱导型一氧化氮合酶（eNOS 和 iNOS）蛋白表达，以及评估大鼠前脑的氧化应激相关生化参数，来研究奈必洛尔的作用。此外，还检测了脑梗死体积和前脑的组织病理学变化。
奈必洛尔呈剂量依赖性地增加 eNOS 表达，同时降低 iNOS 表达。此外，奈必洛尔抑制了缺血/再灌注诱导的还原型谷胱甘肽水平的耗竭，并降低了升高的总一氧化氮终产物和丙二醛水平、超氧化物歧化酶和乳酸脱氢酶活性。一个值得注意的发现是，无论是否发生缺血/再灌注损伤或奈必洛尔治疗，过氧化氢酶活性均未发生变化。然而，结果证实奈必洛尔可显著减少梗死体积，并减轻缺血/再灌注引起的组织病理学变化。
本研究表明奈必洛尔对脑缺血/再灌注损伤具有神经保护作用。奈必洛尔观察到的神经保护作用可能通过调节 eNOS 和 iNOS 的表达以及抑制氧化应激诱导的损伤来解释。因此，奈必洛尔可能被认为是易患中风的患者的潜在治疗候选药物。
