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肥胖症通过氧化应激激活PARP1/NAD+/SIRT1轴,从而加剧术后认知功能障碍

Li Xu¹, Yuanyuan Ma¹, Yelong Ji¹

¹Department of Anesthesia, Zhongshan Hospital, Fudan University, No. 180 Fenglin Road, Shanghai 200032, China.

Experimental gerontology

|November 4, 2024

概括

肥胖会通过增加氧化应激和激活PARP1/NAD+/SIRT1通路而使术后认知功能障碍 (POCD) 恶化. 这项研究揭示了高脂肪饮食如何损害小鼠手术后的记忆力.

科学领域:

神经科学是一个神经科学.
代谢障碍代谢障碍代谢障碍
手术研究的研究.

背景情况:

手术后认知功能障碍 (POCD) 是手术后的一个重大问题.
肥胖越来越被认为是影响手术结果的潜在风险因素.
将肥胖与恶化的POCD联系在一起的确切机制仍然不完全理解.

研究的目的:

调查肥胖对POCD发展的影响.
阐明肥胖导致POCD恶化背后的分子机制.

主要方法:

在使用高脂肪饮食的小鼠中建立了肥胖模型.
通过在异花麻醉下内部固定骨折来创建POCD动物模型.
使用莫里斯水迷宫评估认知功能;通过免疫光分析海马氧化应激和分子通路 (PARP1,NAD+/NADH,SIRT1);在体外研究中使用暴露于棕酸的HT22细胞.

主要成果:

与对照人群相比,肥胖小鼠在手术后表现出学习和记忆障碍.
肥胖加剧了麻醉和手术诱导的氧化应激在海马.
肥胖导致PARP1表达增加,NAD+/NADH比和SIRT1表达减少,与激活PARP1/NAD+/SIRT1轴的体外发现一致.

结论:

肥胖可能会通过促进海马氧化应激来加剧POCD.
PARP1/NAD+/SIRT1轴的激活似乎是中介肥胖对手术后认知功能的负面影响的关键机制.
针对这种途径可以提供治疗策略,以预防肥胖患者的POCD.

关键词:

这是NAD (((+)肥胖问题肥胖问题氧化应激是一种氧化应激.PARP1 的第一部分.手术后的认知功能障碍一个SIRT1系统.

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