<br>慢性睡眠剥夺模型中氧化应激与 Aβ 积累相关,Brain Research

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慢性睡眠剥夺模型中氧化应激与 Aβ 积累相关
Brain Research ( IF 2.7 ) Pub Date : 2024-01-20 , DOI: 10.1016/j.brainres.2024.148776
Zhao Beiyu ₁ , Zhou Rong ₁ , Zhao Yi ₁ , Wei Shan ₁ , Liu Peng ₂ , Wei Meng ₁ , Peng Wei ₁ , Yuan Ye ₁ , Qu Qiumin ₁

Affiliation

β淀粉样蛋白（Aβ）积累是阿尔茨海默病（AD）的主要病理变化，是大脑中Aβ产生和清除失衡所致。我们前期的研究发现，慢性睡眠剥夺（CSD）通过破坏Aβ产生和清除的平衡，导致Aβ在大脑中沉积，但具体机制尚不清楚。在本研究中，我们研究了氧化应激对 CSD 大鼠 Aβ 积累的影响。我们发现，CSD 后，大脑中活性氧 (ROS) 和丙二醛 (MDA) 的水平显着升高，而超氧化物歧化酶 (SOD) 水平下降。此外，CSD 后血清 ROS 升高，SOD 下降。大脑氧化应激水平与β位APP裂解酶1（BACE1）、低密度脂蛋白受体相关蛋白1（LRP1）和晚期糖基化终末产物受体（RAGE）水平显着相关。海马和前额叶的血清氧化介质浓度与血浆可溶性LRP1（sLRP1）和可溶性RAGE（sRAGE）水平密切相关。这些结果表明大脑和血清中的氧化应激可能参与了 CSD 诱导的 Aβ 积累。潜在的机制可能与破坏 Aβ 产生和清除的平衡有关。

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Oxidative stress is associated with Aβ accumulation in chronic sleep deprivation model

Amyloid-β (Aβ) accumulation is the main pathological change in Alzheimer's disease (AD), which results from the imbalance of production and clearance of Aβ in the brain. Our previous study found that chronic sleep deprivation (CSD) led to the deposition of Aβ in the brain by disrupting the balance of Aβ production and clearance, but the specific mechanism was not clear. In the present study, we investigated the effects of oxidative stress on Aβ accumulation in CSD rats. We found that the levels of reactive oxygen species (ROS) and malondialdehyde (MDA) significantly increased after CSD, while superoxide dismutase (SOD) decreased in the brain. Furthermore, the serum ROS was elevated and SOD declined after CSD. The levels of oxidative stress in the brain were significantly correlated with β-site APP-cleaving enzyme 1 (BACE1), low-density lipoprotein receptor-related protein-1 (LRP1), and receptor of advanced glycation end products (RAGE) levels in hippocampus and prefrontal lobe, and the concentration of serum oxidative mediators were strongly correlated with plasma levels of soluble LRP1 (sLRP1) and soluble RAGE (sRAGE). These results suggested that the oxidative stress in the brain and serum may involved in the CSD-induced Aβ accumulation. The underlying mechanism may be associated with disrupting the balance of Aβ production and clearance.

更新日期：2024-01-20

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