| 常亚娟,黄树明,湛清扬,吴 丹,张 博.基于NF-κB/HIF-1α信号通路探讨慢性脑低灌注与神经炎症的相关性研究[J].,2024,(11):2038-2042 |
| 基于NF-κB/HIF-1α信号通路探讨慢性脑低灌注与神经炎症的相关性研究 |
| Research on The Correlation between Chronic Cerebral Hypoperfusion and Neuritis Based on NF-κB/HIF-1α Signaling Pathway |
| 投稿时间：2024-01-28 修订日期：2024-02-23 |
| DOI：10.13241/j.cnki.pmb.2024.11.007 |
| 中文关键词: 慢性脑低灌注 NF-κB HIF-1α 神经炎症 |
| 英文关键词: Chronic cerebral hypoperfusion NF-κB HIF-1α Neuroinflammation |
| 基金项目:国家自然科学基金面上项目(81873108）；黑龙江省卫健委科研课题（20211313010353）；黑龙江省中医药科研项目（ZHY19-012，ZHY2022-118）； 黑龙江中医药大学科研基金项目（2019BJP02） |
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| 中文摘要: |
| 摘要 目的：探究NF-κB/HIF-1α信号通路在慢性脑低灌注引起神经炎症过程中的作用及机制。方法：采用单侧颈总动脉永久性结扎（Unilateral Common Carotid Artery Occlusion，UCCAO）方法建立慢性脑低灌注小鼠模型，随机分为3大组，每组50只，分别为正常对照组，假手术组和UCCAO组，每大组按1 d、3 d、7 d、14 d、21 d分为5小组。采用Morris水迷宫评定学习记忆能力。采用RT-PCR法检测小鼠脑组织HIF-1α mRNA和NF-κB p65 mRNA相对表达水平。采用ElISA 方法检测小鼠脑组织炎症指标TNF-α、IL-1β。结果：与假手术组比较，UCCAO组学习记忆明显下降（P<0.01）。与假手术组比较，UCCAO组小鼠脑组织HIF-1α mRNA和NF-κB p65 mRNA相对表达水平明显增加（P<0.01），HIF-1α mRNA和NF-κB p65 mRNA相对表达水平均于术后3 d开始明显增加，7 d出现高峰，且21 d后相对表达水平仍然明显增加（P<0.01）。与假手术组比较，UCCAO组小鼠脑组织匀浆液中TNF-α和IL-1β的含量明显增加（P<0.01）。结论：1.慢性持续性脑低灌注可导致小鼠出现进行性认知功能障碍。2.CCH后缺血缺氧既可以激活HIF-1α信号通路,又是NF-κB信号转导途径的刺激因子，这两条信号通路存在着诸多交叉，NF-κB活化对HIF-1α调控和炎症反应的形成正反馈。 |
| 英文摘要: |
| ABSTRACT Objective: To explore the role and mechanism of NF-κB / HIF-1α signaling pathway in the neuroinflammation caused by chronic cerebral hypoperfusion. Methods: The chronic cerebral hypoperfusion mouse model was established by unilateral common carotid artery ligation (Unilateral Common Carotid Artery Occlusion UCCAO), randomly divided into 3 large groups of 50 mice, normal control group, sham group and UCCAO group. Each large group was divided into 5 groups according to 1 d, 3 d, 7 d, 14 d and 21 d. Learning and memory abilities were assessed using the Morris water maze. The relative expression levels of HIF-1α mRNA and NF-κB p65 mRNA in mouse brain tissues were determined by RT-PCR. TNF-α and IL-1β were detected by ElISA. Results: Compared with the sham group, learning and memory was significantly decreased in the UCCAO group (P<0.01). Compared with the sham group, the relative expression levels of HIF-1α mRNA and NF-KBp65 mRNA in UCCAO mice increased significantly (P<0.01), while the relative expression levels of HIF-1α mRNA and NF-κB p65 mRNA increased significantly from 3 d and peaked at 7 d, and the relative expression level still increased significantly after 21d (P<0.01). Compared with the sham group, TNF-α and IL-1β were significantly increased in the UCCAO group (P<0.01). Conclusion: 1. Chronic persistent cerebral hypoperfusion can lead to progressive cognitive dysfunction in mice. 2. Ischia and hypoxia after CCH can not only activate HIF-1α signaling pathway, but also be a stimulating factor of NF-κB signal transduction pathway. These two signaling pathways have many intersections, and NF-κB activation provides positive feedback on the regulation of HIF-1α and the formation of inflammatory response. |
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