慢性间断缺氧通过上调大鼠海马HMGB1和NF-κB损伤学习记忆  

Chronic intermittent hypoxia impairs learning and memory by upregulating HMGB1 and NF-κB in rat hippocampus

作　　者：吴振纲 肖尧 陈雅芳[2] 张金英[2] 郭泽铭 林君 杨美丽[2] WU Zhengang;XIAO Yao;CHEN Yafang;ZHANG Jinying;GUO Zeming;LIN Jun;YANG Meili(Department of Surgery,Quanzhou Medical College,Quanzhou 362000;Department of Neurology,the Second Affiliated Hospital of Fujian Medical University,Quanzhou 362000,China)

机构地区：[1]泉州医学高等专科学校外科教研室,泉州362000 [2]福建医科大学附属第二医院神经内科,泉州362000

出　　处：《神经解剖学杂志》2024年第2期224-230,共7页Chinese Journal of Neuroanatomy

基　　金：福建省自然科学基金(2020J01226);福建省卫生健康科技计划(2022GGB005)。

摘　　要：目的:探索慢性间断缺氧(CIH)导致大鼠学习记忆功能障碍,以及对海马区高迁移率族蛋白1(HMGB1)和核转录因子-κB(NF-κB)表达的影响。方法:制作CIH大鼠模型,40只SD大鼠分为常氧组(normoxia)、缺氧4周组(CIH4组)、缺氧8周组(CIH8组)和缺氧12周组(CIH12组)。采用Morris水迷宫评估大鼠学习记忆能力,免疫组织化学染色和ELISA法检测大鼠海马区HMGB1和NF-κB的表达。结果:与常氧组相比,CIH12和CIH8组的逃避潜伏期延长,穿越平台次数和平台所在象限停留时间显著缩短,CIH4组的无显著差异。另外,常氧组海马区HMGB1和NF-κB的表达未见明显表达,CIH4组可见少许表达,CIH8组和CIH12组可见明显表达,同时CIH12组的表达显著高于CIH8组。结论:CIH可导致大鼠的学习记忆功能下降,且间断缺氧时间越长对其学习记忆功能的影响越显著。此外,CIH还导致海马区HMGB1和NF-κB的表达水平升高,并且缺氧12周比8周增加更为明显。Objective:To explore the effect of chronic intermittent hypoxia(CIH)on learning and memory dysfunction in rats,as well as the expression of high mobility group box-1(HMGB1)and nuclear transcription factor-κB(NF-κB)in the hippocampus region.Methods:The CIH rat model was established,and forty SD rats were randomly divided into four groups:normoxia group,hypoxia for 4 weeks group(CIH4 group),hypoxia for 8 weeks group(CIH8 group),and hypoxia for 12 weeks group(CIH12 group).Morris water maze was used to assess the learning memory ability of rats,and immunohistochemistry and ELISA were used to detect the expression of HMGB1 and NF-κB in the hippocampus of rats.Results:Compared with the normoxia group,the CIH12 and CIH8 groups had longer escape latency,the number of crossing the platform and the residence time in the quadrant of the platform were significantly shortened,but there was no significant difference in the CIH4 group.Additionally,there was no significant expression of HMGB1 and NF-κB in the hippocampal region of the normoxia group,but little expression was observed in CIH4 group,and significantly expressed in CIH8 group and CIH12 group,and the expression of CIH12 group was significantly higher than that of CIH8 group.Conclusion:CIH can lead to a decline in learning and memory function in rats,and the longer time of intermittent hypoxia led to the more significant effect on their learning and memory function.In addition,CIH also leads to increased expression levels of HMGB1 and NF-κB in the hippocampus region,and the expression increased more significantly after hypoxia for 12 weeks,comparing to hypoxia for 8 weeks.

关 键 词：慢性间断缺氧 高迁移率族蛋白1 核转录因子-ΚB 学习记忆 海马 大鼠 

分 类 号：R766[医药卫生—耳鼻咽喉科]