orexin-A 通过激活 Nrf2/HO-1 信号通路减轻创伤性脑损伤中的铁死亡。
Orexin-A alleviates ferroptosis by activating the Nrf2/HO-1 signaling pathway in traumatic brain injury.
机构信息
Department of Rehabilitation Medicine, First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, PR China.
First Department of Rehabilitation Medicine, Affiliated Hospital of Jiangxi University of Traditional Chinese Medicine, Nanchang, Jiangxi 330006, China.
出版信息
Aging (Albany NY). 2024 Feb 12;16(4):3404-3419. doi: 10.18632/aging.205541.
BACKGROUND
Traumatic Brain Injury (TBI) has high disability and mortality rate. Oxidative stress and ferroptosis are important pathophysiological characteristics after TBI. Orexin-A (OXA) can alleviate neuronal damage in diverse neurological disorders. Nevertheless, the role and mechanism of OXA in TBI stay unknown.
OBJECTIVES
The research investigated protection influence of OXA on TBI and its potential mechanisms.
METHODS
Male Sprague-Dawley rats were randomly grouped into: sham, TBI, TBI + normal saline (NS) and TBI+OXA groups. TBI model was constructed in rat via modified Feeney's approach, and OXA treatment was administered following construction of TBI model.
RESULTS
Relative to TBI+NS group, TBI+OXA group displayed greatly recovered tissue damage and neurological deficits. Additionally, OXA eased oxidative stress as well as ferroptosis in cerebral cortex of rats following TBI. Furthermore, OXA increased Nrf2 expression and regulating factors HO-1 and NQO1 in cerebral cortex of TBI rats.
CONCLUSIONS
Our research found OXA may restrain ferroptosis via Nrf2/HO-1 signaling pathway activation, thereby reducing brain injury after TBI.
背景
创伤性脑损伤（TBI）具有高残疾率和死亡率。氧化应激和铁死亡是 TBI 后的重要病理生理特征。食欲素-A（OXA）可以减轻多种神经疾病中的神经元损伤。然而，OXA 在 TBI 中的作用和机制尚不清楚。
目的
本研究旨在探讨 OXA 对 TBI 的保护作用及其潜在机制。
方法
雄性 Sprague-Dawley 大鼠随机分为：假手术组、TBI 组、TBI+生理盐水（NS）组和 TBI+OXA 组。通过改良的 Feeney 方法构建大鼠 TBI 模型，并在构建 TBI 模型后给予 OXA 治疗。
结果
与 TBI+NS 组相比，TBI+OXA 组的组织损伤和神经功能缺损明显恢复。此外，OXA 减轻了 TBI 后大鼠大脑皮质的氧化应激和铁死亡。此外，OXA 增加了 TBI 大鼠大脑皮质中 Nrf2 及其调节因子 HO-1 和 NQO1 的表达。
结论
本研究发现，OXA 可能通过激活 Nrf2/HO-1 信号通路来抑制铁死亡，从而减轻 TBI 后的脑损伤。
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