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白藜芦醇减轻帕金森病大鼠模型中 6-羟多巴胺诱导的氧化损伤和多巴胺耗竭。

Resveratrol attenuates 6-hydroxydopamine-induced oxidative damage and dopamine depletion in rat model of Parkinson's disease.

机构信息

Department of Medical Elementology & Toxicology, Jamia Hamdard (Hamdard University), Hamdard Nagar, New Delhi, India.

出版信息

Brain Res. 2010 Apr 30;1328:139-51. doi: 10.1016/j.brainres.2010.02.031. Epub 2010 Feb 16.

Abstract

The present study was undertaken to investigate the neuroprotective effects of resveratrol (RES) on 6-hydroxydopamine (6-OHDA)-induced Parkinson's disease (PD) in rats. PD is an age-related neurodegenerative disorder in which the role of reactive oxygen species (ROS) is strongly implicated. RES, a polyphenolic antioxidant compound enriched in grapes, has been shown to have antioxidant and anti-inflammatory actions and thus was tested for its beneficial effects using 6-OHDA-induced PD rat model. Male Wistar rats were pretreated with RES (20mg/kg body weight i.p.) once daily for 15 days and subjected to unilateral intrastriatal injection of 6-OHDA (10 microg in 0.1% ascorbic acid in normal saline). Three weeks after 6-OHDA infusion, rats were tested for neurobehavioral activity and were killed after 4 weeks of 6-OHDA infusion for the estimation of lipid peroxidation, glutathione content, and activity of antioxidant enzymes (glutathione peroxidase [GPx], glutathione reductase [GR], catalase [CAT], and superoxide dismutase [SOD]. RES was found to be successful in upregulating the antioxidant status and lowering the dopamine loss. Conversely, the elevated level of thiobarbituric acid reactive substances (TBARS), protein carbonyl (PC), and activity of phospholipase A2 in 6-OHDA group was attenuated significantly in RES-pretreated group when compared with 6-OHDA-lesioned group. These results were supported by the immunohistochemical findings in the substantia nigra that has shown the protection of neurons by RES from deleterious effects of 6-OHDA. Thus, RES may be used to reduce the deterioration caused by free radicals thereby preventing subsequent behavioral, biochemical, and histopathological changes that occur during PD.

摘要

本研究旨在探讨白藜芦醇(RES)对大鼠 6-羟多巴胺(6-OHDA)诱导的帕金森病(PD)的神经保护作用。PD 是一种与年龄相关的神经退行性疾病,其中活性氧(ROS)的作用被强烈暗示。RES 是一种富含葡萄的多酚抗氧化剂化合物,已被证明具有抗氧化和抗炎作用,因此使用 6-OHDA 诱导的 PD 大鼠模型来测试其有益作用。雄性 Wistar 大鼠每天腹腔注射 RES(20mg/kg 体重)预处理 15 天,并接受单侧纹状体注射 6-OHDA(0.1%抗坏血酸中的 10μg 在生理盐水)。6-OHDA 输注 3 周后,对大鼠进行神经行为活性测试,并在 6-OHDA 输注 4 周后杀死大鼠,以估计脂质过氧化、谷胱甘肽含量和抗氧化酶(谷胱甘肽过氧化物酶 [GPx]、谷胱甘肽还原酶 [GR]、过氧化氢酶 [CAT] 和超氧化物歧化酶 [SOD] 的活性。RES 成功地上调了抗氧化状态并降低了多巴胺的损失。相反,与 6-OHDA 损伤组相比,在 RES 预处理组中,6-OHDA 组中的硫代巴比妥酸反应物质(TBARS)、蛋白质羰基(PC)和磷脂酶 A2 活性升高得到显著降低。这些结果得到了黑质中免疫组织化学发现的支持,该发现表明 RES 可保护神经元免受 6-OHDA 的有害影响。因此,RES 可用于减少自由基引起的恶化,从而防止 PD 期间发生的后续行为、生化和组织病理学变化。

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