Protective Effect of Luteolin in Experimental Ischemic Stroke: Upregulated SOD1, CAT, Bcl-2 and Claudin-5, Down-Regulated MDA and Bax Expression
Protective Effect of Luteolin in Experimental Ischemic Stroke: Upregulated SOD1, CAT, Bcl-2 and Claudin-5, Down-Regulated MDA and Bax Expression
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DOI：
10.1007/s11064-012-0822-1
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发表时间：
2012-09-01
影响因子：
4.4
通讯作者：
Li, Yanhua
中科院分区：
文献类型：
--
作者：
Qiao, Huimin;Dong, Lipeng;Li, Yanhua
木犀草素最近被证明通过其抗氧化和抗细胞凋亡的特性而产生了一系列的生物学效应。氧化和细胞凋亡损伤在脑缺血发病机制中起重要作用，可能成为治疗的靶点。本研究旨在探讨木犀草素对脑缺血的神经保护作用及其机制。采用永久性大脑中动脉闭塞(PMCAO)法制备局灶性脑缺血模型。PMCAO后即刻分别给予不同剂量的木犀草素10 mg/kg和25 mg/kg腹腔注射。实验一，分析木犀草素的神经保护作用。分别于术后24和72h测定神经功能、脑含水量和脑梗塞体积。用免疫组织化学、Western印迹和逆转录聚合酶链式反应检测SOD1、Bcl2和Bax的表达。实验二，对木犀草素的抗氧化活性进行了评价。用分光光度计法测定超氧化物歧化酶、过氧化氢酶活性和丙二醛含量。实验三，检测木犀草素对Claudin-5表达的影响。与MCAO组比较，木犀草素能显著提高SOD1、CAT、Bcl2和claudin-5的活性(P<；0.05)，降低MDA和Bax的水平(P<；0.05)，减轻神经功能缺失、脑梗塞体积和脑含水量(P<；0.05)。结果表明，木犀草素对脑缺血损伤具有保护作用，其机制可能与减轻氧化应激和细胞凋亡，上调claudin-5的表达有关。
Luteolin recently has been proved to elicit a vanity of biological effects through its antioxidant and anti-apoptosis properties. Oxidative and apoptosis damage play an important role in cerebral ischemic pathogenesis and may represent a target for treatment. The aim of this study was to evaluate the neuroprotective effects of luteolin and the underlying mechanisms in cerebral ischemia. Focal cerebral ischemia was induced in adult male Sprague-Dawley rats by permanent middle cerebral artery occlusion (pMCAO). Luteolin was injected intraperitoneally at different doses of 10 or 25 mg/kg immediately after pMCAO. Experiment 1, luteolin's neuroprotective effect was analyzed. Neurological deficits, brain water content and infarct volume were evaluated at 24 and 72 h after pMCAO. SOD1, Bcl-2, and Bax expression were measured by immunohistochemistry, western blot and reverse transcription-polymerase chain reaction. Experiment 2, luteolin's anti-oxidative activities were evaluated. SOD1, CAT activities, and MDA content were measured by spectrophotometer. Experiment 3, the influence of luteolin on claudin-5 was detected. Compared with MCAO group, luteolin significantly increased the activities of SOD1, CAT, Bcl-2 and claudin-5 (P < 0.05), decreased the levels of MDA and Bax (P < 0.05), and alleviated the neurological deficits, infarct volume and brain water content (P < 0.05). The results indicated that luteolin protected the brain from ischemic damage, and this effect may be through reduction of oxidative stress and apoptosis, and upregulation of the expressions of claudin-5.