Neuroprotection of hydroxysafflor yellow A in the transient focal ischemia: Inhibition of protein oxidation/nitration, 12/15-lipoxygenase and blood-brain barrier disruption
Neuroprotection of hydroxysafflor yellow A in the transient focal ischemia: Inhibition of protein oxidation/nitration, 12/15-lipoxygenase and blood-brain barrier disruption
复制标题
羟基红花黄 A 在短暂性局部缺血中的神经保护作用：抑制蛋白质氧化/硝化、12/15-脂氧合酶和血脑屏障破坏
DOI：
10.1016/j.brainres.2012.07.047
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发表时间：
2012-09-14
期刊：
影响因子：
2.9
通讯作者：
Cheng, Yan
中科院分区：
文献类型：
--
作者：
Sun, Li;Yang, Li;Cheng, Yan
羟基红花黄色素A(HSYA)是红花黄色素的主要成分，是红花小花的水提物。我们报道了一项评价HSYA对大鼠大脑中动脉闭塞(60分钟)和再灌注(24小时)的神经保护作用的实验研究，在此实验模型中发现了过量产生的活性氧和氮物种。在我们的数据中，组织蛋白的生化分析表明，与假手术对照组相比，脑缺血/再灌注(I/R)损伤导致脑组织中羰基和硝基酪氨酸的显著升高，表明脑蛋白质发生了氧化/硝化修饰。I-ISYA处理(1、5和10 mg/kg)可抑制I/R诱导的蛋白质氧化和硝化。12/15-脂氧合酶(12/15-LOX)是参与脑I/R氧化应激的酶，在I/R大鼠脑内呈高表达。HSYA 1、5和10 mg/kg剂量依赖性地抑制12/15-LOX表达和活性的上调，以其代谢物15-羟基二十烷酸-曲烯酸(15-HETE)的水平来评价其活性。此外，HSYA还能显著减轻血脑屏障(BBB)通透性的增加(分别以免疫球蛋白G漏出量、伊文思蓝渗出量和脑含水量为指标)，表明HSYA对脑I/R损伤后血脑屏障破坏和脑水肿具有保护作用。综上所述，这些结果证明了HSYA的神经保护特性，这可能至少部分是因为它有可能减少蛋白质的氧化和硝化，抑制12/15-LOX的上调，并减弱BBB的分解。(C)2012爱思唯尔B.V.保留所有权利。
Hydroxysafflor yellow A (HSYA) is the main component of the safflower yellow pigments, the aqueous extract of safflower florets. We report here an experimental study for evaluating HSYA for their neuroprotective qualities on rats subjected to middle cerebral artery occlusion (60 min) and reperfusion (24 h), an experimental model in which excessive production of reactive oxygen and nitrogen species has been found. In our data, biochemical analysis of tissue proteins showed that cerebral ischemia/reperfusion (I/R) injury resulted in significant elevation of carbonyl groups and nitrotyrosine in the brain of I/R in comparison to sham controls, indicating the occurrence of oxidative/nitrative modification to brain proteins. I-ISYA-treatment (1, 5 and 10 mg/kg) inhibited I/R-induced protein oxidation and nitration. 12/15-Lipoxygenase (12/15-LOX), the enzyme implicated in oxidative stress of cerebral I/R, displayed overexpression in I/R rats. Elevated 12/15-LOX activity, estimated by the level of its metabolite 15-hydroxyeicosate-traenoic acid (15-HETE), was also induced by the challenge of cerebral I/R Administration of HSYA 1, 5 and 10 mg/kg reduced the upregulation of 12/15-LOX expression and activity in a dose-dependent manner. Moreover, the increase in blood-brain barrier (BBB) permeability evaluated by IgG leakage, Evans blue extravasation, and brain water content, respectively, was markedly alleviated by HSYA, indicating its protection against BBB disruption and brain edema following I/R insult. Taken together, these results demonstrate the neuroprotective properties of HSYA, which may be at least in part due to its potential to reduce protein oxidation and nitration, inhibit the upregulation of 12/15-LOX, and attenuate BBB breakdown. (C) 2012 Elsevier B.V. All rights reserved.