Research on The Correlation between Chronic Cerebral Hypoperfusion and Neuritis Based on NF-κB/HIF-1α Signaling Pathway
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 E1ISA.Results:Compared with the sham group,learning and memory was significantly decreased in the UCCAO group(PP＜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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