Apolipoprotein E Deficiency Exacerbates Spinal Cord Injury in Mice: Inflammatory Response and Oxidative Stress Mediated by NF-κB Signaling Pathway.
Apolipoprotein E Deficiency Exacerbates Spinal Cord Injury in Mice: Inflammatory Response and Oxidative Stress Mediated by NF-κB Signaling Pathway.
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载脂蛋白 E 缺乏加剧小鼠脊髓损伤：NF-kappa B 信号通路介导的炎症反应和氧化应激
DOI：
10.3389/fncel.2018.00142
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发表时间：
2018
影响因子：
5.3
通讯作者：
Liu C
中科院分区：
文献类型：
--
作者：
Yang X;Chen S;Shao Z;Li Y;Wu H;Li X;Mao L;Zhou Z;Bai L;Mei X;Liu C
脊髓损伤（Spinal cord injury，SCI）是一种严重的神经系统损伤，涉及复杂的病理过程.炎症反应和氧化应激在二次损伤中普遍存在，并影响SCI的功能恢复。特别是载脂蛋白E（Apoprotein E，APOE）可诱导神经元的修复和再生，而ApoE的缺乏会损害脊髓血屏障，降低脊髓损伤后的功能恢复。然而，ApoE介导SCI炎症反应和氧化应激信号通路的机制仍然很难理解。本研究旨在探讨脊髓损伤急性期ApoE缺乏依赖性炎症反应和氧化应激的信号通路。在本研究中，与野生型小鼠相比，Apoe−/−小鼠在SCI后延迟了功能恢复，并且具有更大的病变尺寸。此外，ApoE缺乏通过增加白细胞介素-6（IL-6）和白细胞介素-1 β（IL-1β）的表达诱导过度的炎症反应，并通过减少Nrf 2和HO-1的表达增加氧化应激。此外，缺乏ApoE促进神经细胞凋亡和减少神经元数目在脊髓前角SCI后。从机制上讲，我们发现ApoE的缺失通过激活SCI后NF-κB增加了炎症和氧化应激。相反，核因子-κB（NF-κB;吡咯烷二硫代氨基甲酸酯）的抑制剂可减轻这些变化。总的来说，这些结果表明NF-κB活化在调节ApoE缺乏依赖性炎症和氧化应激中的关键作用对SCI后的恢复是有害的。
Spinal cord injury (SCI) is a severe neurological trauma that involves complex pathological processes. Inflammatory response and oxidative stress are prevalent during the second injury and can influence the functional recovery of SCI. Specially, Apolipoprotein E (APOE) induces neuronal repair and nerve regeneration, and the deficiency of Apoe impairs spinal cord-blood-barrier and reduces functional recovery after SCI. However, the mechanism by which Apoe mediates signaling pathways of inflammatory response and oxidative stress in SCI remains largely elusive. This study was designed to investigate the signaling pathways that regulate Apoe deficiency-dependent inflammatory response and oxidative stress in the acute stage of SCI. In the present study, Apoe−/− mice retarded functional recovery and had a larger lesion size when compared to wild-type mice after SCI. Moreover, deficiency of Apoe induced an exaggerated inflammatory response by increasing expression of interleukin-6 (IL-6) and interleukin-1β (IL-1β), and increased oxidative stress by reducing expression of Nrf2 and HO-1. Furthermore, lack of Apoe promoted neuronal apoptosis and decreased neuronal numbers in the anterior horn of the spinal cord after SCI. Mechanistically, we found that the absence of Apoe increased inflammation and oxidative stress through activation of NF-κB after SCI. In contrast, an inhibitor of nuclear factor-κB (NF-κB; Pyrrolidine dithiocarbamate) alleviates these changes. Collectively, these results indicate that a critical role for activation of NF-κB in regulating Apoe-deficiency dependent inflammation and oxidative stress is detrimental to recovery after SCI.
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影响因子：
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DOI：
10.1093/brain/aww039
发表时间：
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期刊：
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影响因子：
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