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-1αSignaling Pathway

作　　者：常亚娟[1,2] 黄树明 湛清扬[1] 吴丹 张博[1] CHANG Ya-juan;HUANG Shu-ming;ZHAN Qing-yang;WU Dan;ZHANG Bo(Heilongjiang University of Traditional Chinese Medicine,Harbin,Heilongjiang,150040,China;The Second Affiliated Hospital of Heilongjiang University of Traditional Chinese Medicine,Harbin,Heilongjiang,150001,China)

机构地区：[1]黑龙江中医药大学,黑龙江哈尔滨150040 [2]黑龙江中医药大学附属第二医院,黑龙江哈尔滨150001

出　　处：《现代生物医学进展》2024年第11期2038-2042,2119,共6页Progress in Modern Biomedicine

基　　金：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)。

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 m RNA和NF-κB p65 m RNA相对表达水平。采用El ISA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-1αm RNA和NF-κB p65 m RNA相对表达水平明显增加(P<0.01),HIF-1α m RNA和NF-κB p65 m RNA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。Objective:To explore the role and mechanism of NF-κB/HIF-1αsignaling 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-1αmRNA and NF-κB p65 mRNA in mouse brain tissues were determined by RT-PCR.TNF-αand IL-1βwere 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-1αmRNA and NF-KBp65 mRNA in UCCAO mice increased significantly(P<0.01),while the relative expression levels of HIF-1αmRNA 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-αand IL-1βwere 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-1αsignaling 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-1αand the formation of inflammatory response.

关 键 词：慢性脑低灌注 NF-ΚB HIF-1Α 神经炎症 

分 类 号：R-33[医药卫生] R741.02