河北医科大学学报 ›› 2023, Vol. 44 ›› Issue (10): 1122-1128.doi: 10.3969/j.issn.1007-3205.2023.10.002

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基于TLR4/MyD88信号通路探究miR-326对抑郁模型脑组织的保护作用

  

  1. 河北省衡水市人民医院精神心理科, 河北 衡水 053000

  • 出版日期:2023-10-25 发布日期:2023-11-03
  • 作者简介:刘威(1987-),男,河北衡水人,河北省衡水市人民医院主治医师,医学学士,从事精神心理科疾病诊治研究。
  • 基金资助:
    河北省重点科技研究计划(20181589)

The protective effect of miR-326 on brain tissue in depression models based on TLR4/MyD88 signaling pathway

  1. Department of Psychiatry, Hengshui People′s Hospital, Hebei Province, Hengshui 053000, China

  • Online:2023-10-25 Published:2023-11-03

摘要: 目的 探究抑郁模型脑组织的可能保护机制。
方法 通过不同类型的胁迫建立大鼠慢性不可预知温和应激(chronic unpredictable mild stress,CUMS)抑郁模型,通过侧脑室注射miR-326 agomiR以上调miR-326的表达水平。蔗糖偏好测试(sucrose preference test,SPT)、旷场测试(open field test,OFT)、强迫游泳测试(forced swim test,FST)、高架十字迷宫(elevated plus maze,EPM)实验被用来检测动物的行为学及抑郁状态。通过ELISA试剂盒检测大鼠血清中去甲肾上腺素(norepinephrine,NE)、多巴胺(dopamine,DA)、5-羟色胺(5-hydroxytryptamine,5-HT)水平,采取Western blot法检测大鼠海马组织TLR4、MyD88蛋白水平。
结果 CUMS组大鼠体重、蔗糖消耗量、OFT中心区域停留时间及张开手臂时间低于对照组,FST静止时间明显高于对照组(P<0.05)。CUMS组大鼠海马组织中miR-326表达显著低于对照组,CUMS+agomiR 326组大鼠海马组织中miR-326表达高于CUMS+agomiR NC组(P<0.05)。CUMS+agomiR 326组大鼠体重、蔗糖消耗量、OFT中心区域停留时间及开放臂停留时间显著高于CUMS+agomiR NC组,FST静止时间明显低于CUMS+agomiR NC组(P<0.05)。CUMS组NE、DA和5-HT水平显著低于对照组,CUMS+agomiR 326组NE、DA和5-HT水平显著高于CUMS+agomiR NC组(P<0.05)。CUMS组大鼠TLR4蛋白和MyD88蛋白水平显著高于对照组,CUMS+agomiR 326组大鼠TLR4蛋白和MyD88蛋白水平显著降低(P<0.05)。
结论 在CUMS抑郁模型中,miR-326可能通过调控TLR4/MyD88信号通路参与脑组织的保护作用。


关键词: 抑郁, 慢性不可预知温和应激, 微RNAs

Abstract: Objective To investigate the potential protective effect of miR-326 on brain tissue in depression models. 
Methods A chronic unpredictable mild stress(CUMS)depression model of ratswas established by different types of stress, and miR-326 expression levels were upregulated by miR-326 agomiR injection in the lateral ventricle. Sucrose preference test (SPT), open field test (OFT), forced swim test (FST), and elevated plus maze (EPM) experiments were used to detect the behavioral and depressive states of the animals. The levels of norepinephrine (NE), dopamine (DA), and 5-hydroxytryptamine (5-HT) in rat serum were measured by enzyme-linked immunosorbent assay (ELISA) kits, and the levels of TLR4 and MyD88 protein expression level in hippocampal tissue of rats were measured by Western blot assay. 
Results The body weight, sucrose consumption, residence time in central region of OFT and open arm time of rats in the CUMS group were lower or less than those in the control group, while the resting time in FST was significantly higher than that in the control group (P<0.05). Expression of miR-326 in the hippocampal tissues of rats in the CUMS group was significantly lower than that of the control group, which was higher in the hippocampal tissues of rats in the CUMS+agomiR 326 group than in the CUMS+ agomiR NC group (P<0.05). Body weight, sucrose consumption, residence time in central region of OFT and open arm time were significantly higher in the CUMS+agomiR 326 group than in the CUMS+agomiR NC group, while resting time in FST was significantly lower than that in the CUMS+agomiR NC group (P<0.05). NE, DA, and 5- HT levels were significantly lower in the CUMS group than in control group, and significantly higher in CUMS+agomiR 326 group than in CUMS+agomiR NC group (P<0.05). The levels of TLR4 protein and MyD88 protein in rats were significantly higher in CUMS group than in control group, which, however, were significantly lower in CUMS+agomiR 326 group (P<0.05). 
Conclusion In the CUMS model of depression, miR-326 may exert a protective effect on brain tissue by regulating the TLR4/MyD88 signaling pathway. 


Key words: depression, chronic unpredictable mild stress, microRNAs