染色域Y样蛋白介导的组蛋白巴豆酰化与抑郁小鼠模型中NGF和炎症因子水平及神经功能紊乱的关系  

The Relationship between Histone Crotonylation Mediated by Chromodomain Y-like Protein and the Levels of NGF,Inflammatory Factors and Neurological Dysfunction in a Mouse Model of Depression

作　　者：张欢[1] 郭改艳[2] 黄娜 马新欣[1] 朱梅 刘亚楠 ZHANG Huan;GUO Gai-yan;HUNAG Na;MA Xin-xin;ZHU Mei;LIU Ya-nan(Department of Psychiatry,The Second Affiliated Hospital of Xi’an Jiaotong University School of Medicine,Xi'an,Shaanixi,710004,China;Department of Neurology,Affiliated Hospital of Yan’an University,Xi'an,Shaanixi,716000,China;Central Laboratory of the Second Affiliated Hospital of Xi’an Jiaotong University School of Medicine,Xi'an,Shaanixi,710004,China;Department of Psychiatry,The First Affiliated Hospital of Xi’an Jiaotong University School of Medicine,Xi'an,Shaanixi,710061,China)

机构地区：[1]西安交通大学医学院第二附属医院心理精神科,陕西西安710004 [2]延安大学附属医院神经内科,陕西延安716000 [3]西安交通大学医学院第二附属医院中心实验室,陕西西安710004 [4]西安交通大学医学院第一附属医院精神心理科,陕西西安710061

出　　处：《现代生物医学进展》2022年第13期2422-2426,共5页Progress in Modern Biomedicine

基　　金：陕西省重点研发计划项目(2020SF-078)。

摘　　要：目的:探究染色域Y样蛋白介导的组蛋白巴豆酰化与抑郁小鼠模型中神经生长因子(Nerve growth factor,NGF)和炎症因子水平及神经功能紊乱的关系。方法:32只成年雄性C57BL/6小鼠分为4组:对照组、模型组、CDYL过表达组、CDYL敲低组,各8只。通过慢性束缚应激诱导抑郁模型,通过旷场试验记录中心时间和中心距离,通过强迫游泳测试记录不动时间。通过RT-qPCR和蛋白质免疫印迹检测CDYL m RNA和蛋白质表达水平。通过ChIP-seq检测组蛋白赖氨酸巴豆酰化。通过ELISA检测TNF-α,IL-1β和IL-6表达水平。通过RT-qPCR检测检测海马组织5-HT和IDO m RNA表达水平。通过蛋免疫组织化学染色检测检测海马组织NGF、BDNF和突触素(Synaptophysin,SYP)表达水平。通过BrdU免疫荧光染色检测神经系统的发育以及识别大脑中的神经发生。结果:模型组中心时间和中心距离较对照组降低,不动时间较对照组升高(P<0.05)。CDYL过表达组中心时间和中心距离较模型组降低,不动时间较模型组升高(P<0.05)。CDYL敲低组中心时间和中心距离较模型组升高,不动时间较模型组降低(P<0.05)。模型组CDYL m RNA和蛋白质表达水平较对照组升高(P<0.05)。CDYL过表达组CDYL m RNA和蛋白质表达水平较模型组升高(P<0.05)。CDYL敲低组TCDYL m RNA和蛋白质表达水平较模型组降低(P<0.05)。模型组组蛋白巴豆酰化水平较对照组降低(P<0.05)。CDYL过表达组组蛋白巴豆酰化水平较模型组降低(P<0.05)。CDYL敲低组组蛋白巴豆酰化较模型组升高(P<0.05)。模型组TNF-α,IL-1β和IL-6表达水平较对照组升高(P<0.05)。CDYL过表达组TNF-α,IL-1β和IL-6表达水平较模型组升高(P<0.05)。CDYL敲低组TNF-α,IL-1β和IL-6表达水平较模型组降低(P<0.05)。模型组5-HT m RNA表达水平较对照组降低,IDO m RNA表达水平较对照组升高(P<0.05)。CDYL过表达组5-HT m RNA表达水平较模型组降低,IDO m RNA表达水平较模型组升�Objective:To explore the relationship between histone crotonylation mediated by staining domain Y-like protein and the levels of nerve growth factor(Nerve growth factor,NGF) and inflammatory factors and neurological disorders in a mouse model of depression.Methods:Thirty-two adult male C57BL/6 mice were divided into 4 groups:control group,model group,CDYL overexpression group,and CDYL knockdown group,with 8 mice in each group.Induce depression model through chronic restraint stress.The center time and center distance were recorded through the open field test,and the immobility time was recorded through the forced swimming test.CDYL m RNA and protein levels were detected by RT-qPCR and Western blotting.The histone lysine crotonylation was detected by ChIP-seq.The levels of TNF-α,IL-1β and IL-6 were detected by ELISA.The levels of 5-HT and IDO m RNA in hippocampus were detected by RT-qPCR.The levels of NGF,BDNF and Synaptophysin(SYP) in hippocampus were detected by egg immunohistochemical staining.Detect the development of the nervous system and identify neurogenesis in the brain by BrdU immunofluorescence staining.Results:The center time and center distance of the model group were lower than control group,and the immobility time was higher than control group(P<0.05).The center time and center distance in the CDYL overexpression group were lower than the model group,and the immobility time was higher than that of the model group(P<0.05).The center time and center distance of the CDYL knockdown group were higher than that of the model group,and the immobility time was lower than that of the model group(P<0.05).The levels of CDYL m RNA and protein in the model group were higher than those in the control group(P<0.05).The levels of CDYL m RNA and protein in the CDYL overexpression group were higher than those in the model group(P<0.05).The levels of TCDYL m RNA and protein in the CDYL knockdown group were lower than those in the model group(P<0.05).The protein crotonylation level of the model group was lower than th

关 键 词：染色域Y样蛋白 组蛋白巴豆酰化 抑郁 神经生长因子 炎症因子 

分 类 号：R-33[医药卫生] R743