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姜黄素激活Wnt/β-连环蛋白信号通路,保护神经元免受间歇性缺氧所致损伤。

Curcumin triggers the Wnt/β-catenin pathway and shields neurons from injury caused by intermittent hypoxia.

作者信息

He Yao, Zhao Yan, Lv Ren-Jun, Dong Na, Wang Xiao, Yu Qin, Yue Hong-Mei

机构信息

The First Clinical Medical College, Lanzhou University, Lanzhou, China.

The First Clinical Medical College, Lanzhou University, Lanzhou, China; Department of Respiratory and Critical Care Medicine, The First Hospital of Lanzhou University, Lanzhou, China.

出版信息

Tissue Cell. 2024 Dec;91:102587. doi: 10.1016/j.tice.2024.102587. Epub 2024 Oct 19.

DOI:10.1016/j.tice.2024.102587
PMID:39454474
Abstract

The objective of this study was to explore the molecular basis through which Curcumin (Cur) mitigates neuronal damage caused by obstructive sleep apnea (OSA). HT22 was used to simulate intermittent hypoxia (IH) injury and explore the effect of Cur on these cells. We evaluated the cell viability, cytotoxicity, apoptosis, proliferation, and Wnt/β-catenin (WβC) pathway. IWR-1 was used to block the pathway and investigate the protective mechanism of Cur. We constructed an in vivo model of IH to validate the results of the cellular experiments. IH accelerated apoptosis and cytotoxicity, suppressed proliferation, and decreased the activity of the WβC pathway. Cur can significantly improve cell viability, reduce apoptosis rate and cell toxicity, promote cell proliferation, and up-regulate the WβC. After blocking the WβC pathway, the proliferative effect of Cur was observably weakened. In vivo, IH caused hippocampal damage and inhibited WβC pathway activity in mice, which was ameliorated by Cur treatment. This implies that Cur could be a novel treatment option for neurological impairment brought on by OSA.

摘要

本研究的目的是探索姜黄素(Cur)减轻阻塞性睡眠呼吸暂停(OSA)所致神经元损伤的分子基础。采用HT22细胞模拟间歇性缺氧(IH)损伤,探讨Cur对这些细胞的影响。我们评估了细胞活力、细胞毒性、凋亡、增殖以及Wnt/β-连环蛋白(WβC)通路。使用IWR-1阻断该通路,并研究Cur的保护机制。我们构建了IH体内模型以验证细胞实验结果。IH加速凋亡和细胞毒性,抑制增殖,并降低WβC通路的活性。Cur可显著提高细胞活力,降低凋亡率和细胞毒性,促进细胞增殖,并上调WβC。阻断WβC通路后,Cur的增殖作用明显减弱。在体内,IH导致小鼠海马损伤并抑制WβC通路活性,而Cur治疗可改善这种情况。这意味着Cur可能是治疗OSA所致神经损伤的一种新选择。

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