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黄芪根囊泡样纳米颗粒通过修复睡眠剥夺小鼠的肠道黏膜屏障和调节氨基酸代谢来改善能量代谢紊乱。

Astragali radix vesicle-like nanoparticles improve energy metabolism disorders by repairing the intestinal mucosal barrier and regulating amino acid metabolism in sleep-deprived mice.

作者信息

Yuan Yue, Gao Wenjing, Gao Yunxiao, Zhang Qiuyan, Shi Yali, Zhang Na, Song Guochao, Hu Longxiao, Jiang Yunyao, Liu Jianxun, Ren Junguo

机构信息

Beijing Key Laboratory of TCM Pharmacology, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, 100091, China.

School of Pharmaceutical Sciences, Tsinghua University, Beijing, 100084, China.

出版信息

J Nanobiotechnology. 2024 Dec 19;22(1):768. doi: 10.1186/s12951-024-03034-x.

Abstract

BACKGROUND

Sleep disorder is widespread and involves a variety of intricate factors in its development. Sleep deprivation is a manifestation of sleep disorder, can lead to energy metabolism disturbances, weakened immune system, and compromised body functions. In extreme situations, sleep deprivation can cause organ failure, presenting significant risks to human health.

PURPOSE

This study aimed to investigate the efficacy and mechanisms of Astragalus Radix vesicles-like nanoparticles (AR-VLNs) in counteracting the deleterious effects of sleep deprivation.

METHODS

The ICR mice were divided into control, model, AR-VLNs high dose (equivalent to 20 g/kg crude drug), AR-VLNs low dose (equivalent to 10 g/kg crude drug), AR high dose (equivalent to 20 g/kg crude drug), and AR low dose (equivalent to 10 g/kg crude drug). The REM (rapid eye movement) sleep-deprivation model was established, and evaluations were conducted for motor function, antioxidant capacity, and energy metabolism indices. Moreover, CACO-2 cells damage was induced with lipopolysaccharide to evaluate the repairing ability of AR-VLNs on the intestinal cell mucosa by measuring permeability. Furthermore, metabolomics was employed to elucidate the mechanisms of AR-VLNs action.

RESULTS

AR-VLNs were demonstrated to enhance the motor efficiency and antioxidant capacity in REM sleep-deprived mice, while also minimized pathological damage and restored the integrity of the intestinal mucosal barrier. In vitro experiments indicated the anti-inflammatory effect of AR-VLNs against LPS-induced cell damage. Additionally, metabolomic analysis linked these effects with regulation of the amino acid metabolic pathways. Further confirmation from molecular biology experiments revealed that the protective effects of AR-VLNs against the deleterious effects of REM sleep deprivation were associated with the restoration of the intestinal mucosal barrier and the enhancement of amino acid metabolism.

CONCLUSION

AR-VLNs administration effectively improved energy metabolism disorders in REM sleep deprived mice, by facilitating the repair of the intestinal mucosal barrier and regulating the amino acid metabolism.

摘要

背景

睡眠障碍普遍存在,其发生涉及多种复杂因素。睡眠剥夺是睡眠障碍的一种表现,可导致能量代谢紊乱、免疫系统减弱和身体机能受损。在极端情况下,睡眠剥夺可导致器官衰竭,对人类健康构成重大风险。

目的

本研究旨在探讨黄芪根囊泡样纳米颗粒(AR-VLNs)对抗睡眠剥夺有害影响的疗效及作用机制。

方法

将ICR小鼠分为对照组、模型组、AR-VLNs高剂量组(相当于20 g/kg生药)、AR-VLNs低剂量组(相当于10 g/kg生药)、AR高剂量组(相当于20 g/kg生药)和AR低剂量组(相当于10 g/kg生药)。建立快速眼动(REM)睡眠剥夺模型,并对运动功能、抗氧化能力和能量代谢指标进行评估。此外,用脂多糖诱导Caco-2细胞损伤,通过测量通透性评估AR-VLNs对肠细胞黏膜的修复能力。此外,采用代谢组学方法阐明AR-VLNs的作用机制。

结果

AR-VLNs被证明可提高REM睡眠剥夺小鼠的运动效率和抗氧化能力,同时还能将病理损伤降至最低,并恢复肠黏膜屏障的完整性。体外实验表明AR-VLNs对脂多糖诱导的细胞损伤具有抗炎作用。此外,代谢组学分析将这些作用与氨基酸代谢途径的调节联系起来。分子生物学实验的进一步证实表明,AR-VLNs对REM睡眠剥夺有害影响的保护作用与肠黏膜屏障的恢复和氨基酸代谢的增强有关。

结论

AR-VLNs给药通过促进肠黏膜屏障的修复和调节氨基酸代谢,有效改善了REM睡眠剥夺小鼠的能量代谢紊乱。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f373/11658387/ebc7f5a40c22/12951_2024_3034_Fig1_HTML.jpg

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