严重缺锌通过FOXO3a/Bax通路介导嗅球神经元凋亡引起嗅觉障碍  

Severe Zinc deficiency causes olfactory malfunction via FOXO3a/Bax pathway-induced olfactory bulb neuronal apoptosis

作　　者：万春华[1] 韩静岭 WAN Chunhua;HAN Jingling(School of Public Health,Nantong University,Nantong 226019;Department of Occupational Health,Radiology and Environmental Hygiene,Xuzhou Center for Disease Control and Prevention,Jiangsu Province)

机构地区：[1]南通大学公共卫生学院,南通226019 [2]江苏省徐州市疾病预防控制中心职业卫生和放射、环境卫生科

出　　处：《南通大学学报（医学版）》2020年第5期406-409,共4页Journal of Nantong University(Medical sciences)

基　　金：国家自然科学基金青年基金资助项目(81300720)。

摘　　要：目的:研究缺锌对嗅球生理的影响及机制,并进一步明确缺锌导致嗅球细胞损伤的分子机制。方法:在大鼠中构建严重和边缘锌缺乏模型,通过食物追踪实验检测缺锌对大鼠嗅觉的影响,进而通过脱氧核苷酸转移酶dUTP缺口末端标记(terminal deoxynucleotidyl transferase dUTP nick end labeling,TUNEL)和免疫组织化学分析锌缺乏对嗅球神经元凋亡的作用,并利用免疫印迹检测相关分子通路的改变。结果:严重锌缺乏可导致大鼠明显的嗅觉障碍,并且在组织病理层面可观察到嗅球神经元的凋亡显著增加,免疫印迹和组化证明叉头框蛋白O3a(forkhead box O3a,FOXO3a)及其下游Bcl-2相关X蛋白(Bcl-2 associated X-protein,Bax)通路发生显著的活化。结论:FOXO3a/Bax通路可能在缺锌诱导的嗅球神经元凋亡中发挥关键作用。Objective:To investigate the impact of Zinc deficiency on olfactory bulb physiology,and further determine the molecular mechanisms underpinning.Methods:A rat model of severe and marginal Zinc deficiency was established.The rat olfactory function was assessed using food pellet chase experiment.Furthermore,terminal deoxynucleotidyl transferase dUTP nick end labeling(TUNEL)and immunohistochemistry was employed to analyze the effect of Zinc deficiency on olfactory bulb neuronal apoptosis.Western Blot analysis was conducted to determine the alterations of related signaling molecules.Results:Severe Zinc deficiency may result in apparent olfactory deficit in rats;we observed that olfactory bulb neuronal apoptosis was significantly elevated at tissue and pathological levels;Western Blot and immunohistochemical assays demonstrated that forkhead box O3a(FOXO3a)and its downstream Bcl-2-associated X-protein(Bax)signaling was markedly activated following Zinc deficiency.Conclusion:FOXO3a/Bax pathway may play a pivotal role in Zinc deficiency-induced olfactory bulb neuronal apoptosis.

关 键 词：锌缺乏 嗅觉 嗅球 神经元凋亡 叉头框蛋白O3a 大鼠 

分 类 号：R151.1[医药卫生—营养与食品卫生学]