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绿茶儿茶素多酚可减轻对间歇性缺氧的行为和氧化反应。

Green tea catechin polyphenols attenuate behavioral and oxidative responses to intermittent hypoxia.

作者信息

Burckhardt Isabel C, Gozal David, Dayyat Ehab, Cheng Yu, Li Richard C, Goldbart Aviv D, Row Barry W

机构信息

Kosair Children's Hospital Research Institute, University of Louisville, 570 South Preston Street, Suite 204, Louisville, KY 40202, USA.

出版信息

Am J Respir Crit Care Med. 2008 May 15;177(10):1135-41. doi: 10.1164/rccm.200701-110OC. Epub 2008 Feb 14.

Abstract

RATIONALE

The intermittent hypoxia (IH) that characterizes sleep-disordered breathing impairs spatial learning and increases NADPH oxidase activity and oxidative stress in rodents. We hypothesized that green tea catechin polyphenols (GTPs) may attenuate IH-induced neurobehavioral deficits by reducing IH-induced NADPH oxidase expression, lipid peroxidation, and inflammation.

OBJECTIVES

To assess the effects of GTP administered in drinking water on the cognitive, inflammatory, and oxidative responses to long-term (>14 d) IH during sleep in male Sprague-Dawley rats.

METHODS

Cognitive assessments were conducted in the Morris water maze. We measured levels and expression of malondialdehyde (MDA), prostaglandin E(2), p47(phox) subunit of NADPH oxidase, receptor for advanced glycation end products (RAGE), and glial fibrillary acidic protein expression in rodent brain tissue.

MEASUREMENTS AND MAIN RESULTS

GTP treatment prevented IH-induced decreases in spatial bias for the hidden platform during the Morris water maze probe trails as well as IH-induced increases in p47phox expression within the hippocampal CA1 region. In untreated animals, IH exposure was associated with doubling of cortical MDA levels in comparison to room air control animals, and GTP-treated animals exposed to IH showed a 40% reduction in MDA levels. Increases in brain RAGE and glial fibrillary acidic protein expression were observed in IH-exposed animals, and these increases were attenuated in animals treated with GTP.

CONCLUSIONS

Oral GTP attenuates IH-induced spatial learning deficits and mitigates IH-induced oxidative stress through multiple beneficial effects on oxidant pathways. Because oxidative processes underlie neurocognitive deficits associated with IH, the potential therapeutic role of GTP in sleep-disordered breathing deserves further exploration.

摘要

原理

以睡眠呼吸障碍为特征的间歇性低氧(IH)会损害啮齿动物的空间学习能力,并增加其NADPH氧化酶活性和氧化应激。我们假设绿茶儿茶素多酚(GTP)可能通过降低IH诱导的NADPH氧化酶表达、脂质过氧化和炎症反应来减轻IH诱导的神经行为缺陷。

目的

评估在雄性Sprague-Dawley大鼠睡眠期间,通过饮水给予GTP对长期(>14天)IH的认知、炎症和氧化反应的影响。

方法

在莫里斯水迷宫中进行认知评估。我们测量了啮齿动物脑组织中丙二醛(MDA)、前列腺素E2、NADPH氧化酶的p47亚基、晚期糖基化终产物受体(RAGE)的水平和表达,以及胶质纤维酸性蛋白的表达。

测量结果与主要结论

在莫里斯水迷宫探测试验中,GTP治疗可防止IH诱导的隐藏平台空间偏差降低,以及IH诱导的海马CA1区域内p47phox表达增加。在未治疗的动物中,与室内空气对照动物相比,IH暴露导致皮质MDA水平加倍,而接受GTP治疗且暴露于IH的动物MDA水平降低了40%。在暴露于IH的动物中观察到脑RAGE和胶质纤维酸性蛋白表达增加,而在接受GTP治疗的动物中这些增加有所减弱。

结论

口服GTP可减轻IH诱导的空间学习缺陷,并通过对氧化途径的多种有益作用减轻IH诱导的氧化应激。由于氧化过程是与IH相关的神经认知缺陷的基础,GTP在睡眠呼吸障碍中的潜在治疗作用值得进一步探索。

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