| 张 欢,郭改艳,黄 娜,马新欣,朱 梅,刘亚楠.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[J].,2022,(13):2422-2426 |
| 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 |
| 投稿时间：2021-11-25 修订日期：2021-12-21 |
| DOI：10.13241/j.cnki.pmb.2022.13.004 |
| 中文关键词: 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 |
| 英文关键词: Staining domain Y-like protein Histone crotonylation Depression Nerve growth factor Inflammatory factor |
| 基金项目:陕西省重点研发计划项目（2020SF-078） |
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| 中文摘要: |
| 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 mRNA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 mRNA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 mRNA和蛋白质表达水平较对照组升高（P<0.05）。CDYL过表达组CDYL mRNA和蛋白质表达水平较模型组升高（P<0.05）。CDYL敲低组TCDYL mRNA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 mRNA表达水平较对照组降低，IDO mRNA表达水平较对照组升高（P<0.05）。CDYL过表达组5-HT mRNA表达水平较模型组降低，IDO mRNA表达水平较模型组升高（P<0.05）。CDYL敲低组5-HT mRNA表达水平较模型组升高，IDO mRNA表达水平较模型组降低（P<0.05）。模型组NGF，BDNF和SYP表达水平较对照组降低（P<0.05）。CDYL过表达组NGF、BDNF和SYP表达水平较模型组降低。CDYL敲低组NGF，BDNF和SYP表达水平较模型组升高（P<0.05）。结论：慢性束缚应激诱导抑郁模型组蛋白巴豆酰化降低、炎症因子水平升高、NGF、BDNF和SYP水平降低以及神经功能紊乱，CDYL过表达组较慢性束缚应模型激进一步加剧炎症反应和神经功能紊乱，而CDYL敲低对慢性束缚应激引起的新生细胞和未成熟神经元损伤具有保护作用。 |
| 英文摘要: |
| ABSTRACT 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 mRNA 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 mRNA 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 mRNA and protein in the model group were higher than those in the control group(P<0.05). The levels of CDYL mRNA and protein in the CDYL overexpression group were higher than those in the model group(P<0.05). The levels of TCDYL mRNA 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 that of the control group(P<0.05). The CDYL overexpression group protein crotonylation level was lower than that of the model group(P<0.05). The protein crotonylation of CDYL knockdown group was higher than that of model group(P<0.05). The levels of TNF-α, IL-1β and IL-6 in the model group were higher than those in the control group (P<0.05). The levels of TNF-α, IL-1β and IL-6 in the CDYL overexpression group were higher than those in the model group (P<0.05). The levels of TNF-α, IL-1β and IL-6 in the CDYL knockdown group were lower than those in the model group (P<0.05). The 5-HT mRNA level of the model group was lower than that of the control group, and the IDO mRNA level was higher than that of the control group(P<0.05). The 5-HT mRNA level in the CDYL overexpression group was lower than that in the model group, and the IDO mRNA level was higher than that in the model group(P<0.05). The 5-HT mRNA level in the CDYL knockdown group was higher than that in the model group, and the IDO mRNA level was lower than that in the model group(P<0.05). The levels of NGF, BDNF and SYP in the model group were lower than those in the control group(P<0.05). The levels of NGF, BDNF and SYP in the CDYL overexpression group were lower than those in the model group. The levels of NGF, BDNF and SYP in the CDYL knockdown group were higher than those in the model group (P<0.05). Conclusion: Chronic restraint stress induces depression model histone crotonylation decreased, inflammatory factor levels increased, NGF, BDNF and SYP levels decreased, and neurological dysfunction. The CDYL overexpression group further aggravated inflammation and nerves than the chronic restraint stress model. Dysfunction, and CDYL knockdown has a protective effect on the damage of new cells and immature neurons caused by chronic restraint stress. |
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