[1]席海龙,黄国哲.Progranulin/TNFR信号通路在焦虑发生发展中的作用研究[J].卒中与神经疾病杂志,2025,32(02):197-204.[doi:10.3969/j.issn.1007-0478.2025.02.015]
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Progranulin/TNFR信号通路在焦虑发生发展中的作用研究()
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《卒中与神经疾病》杂志[ISSN:1007-0478/CN:42-1402/R]

卷:
第32卷
期数:
2025年02期
页码:
197-204
栏目:
论著
出版日期:
2025-04-20

文章信息/Info

文章编号:
1007-0478(2025)02-0197-08
作者:
席海龙黄国哲
473000 河南省南阳市中心医院精神科门诊(席海龙); 南阳市第四人民医院精神六科(黄国哲)
关键词:
颗粒蛋白前体 肿瘤坏死因子-α受体 睡眠剥夺 焦虑样行为 小鼠
分类号:
R74
DOI:
10.3969/j.issn.1007-0478.2025.02.015
文献标志码:
A
摘要:
目的 探讨颗粒蛋白前体(Progranulin,PGRN)/重组人PGRN(Recombinant human progranulin,rhPGRN)/肿瘤坏死因子(Tumor necrosis factor,TNF)-α受体/肿瘤坏死因子受体(Tumor necrosis factor receptor,TNFR)信号通路在睡眠剥夺(Sleep deprivation,S-DEP)诱导的焦虑样行为中的作用。方法 将48只小鼠随机分为3组:对照(Control)组、S-DEP组和S-DEP+重组人PGRN(Recombinant human progranulin,rhPGRN)组,每组各16只; S-DEP组和S-DEP+rhPGRN组小鼠每天21 h不睡觉,持续7 d; 且S-DEP+rhPGRN组在S-DEP前3 d接受脑室内注射重组人PGRN(rhPGRN)治疗; 使用旷场实验(Open-field test,OFT)测试、高架十字迷宫(Elevated plus maze,EPM)测试、明暗盒(Light dark box,LDB)测试、大理石掩埋测试量化小鼠的行为; 通过蛋白质印迹分析和实时荧光定量聚合酶链反应(Real-time quantitative polymerase chain reaction,qPCR)检测PGRN蛋白质和mRNA水平; 免疫荧光染色检测海马亚区小胶质细胞增生; 酶联免疫吸附测定(Enzyme-linked immunosorbent assay,ELISA)试剂盒测量海马匀浆中的促炎因子水平。结果 S-DEP能够在小鼠中诱发明显的焦虑样行为; 生物信息学分析表明S-DEP与脑炎症信号通路之间存在重要关系。与对照组小鼠比较,S-DEP组小鼠海马中PGRN的蛋白(t=3.031,P=0.006)和mRNA(t=3.061,P=0.004)表达水平显著下调; S-DEP+rhPGRN组小鼠在中心停留的时间、行进的总距离和张开双臂中的时间均较S-DEP组明显增加(P<0.05); 施用rhPGRN明显减少S-DEP小鼠海马CA1、CA3和DG区域离子钙结合适配器分子-1(Lonized calcium-binding adapter molecule-1,Iba1)阳性小胶质细胞(P<0.05)以及降低海马匀浆中肿瘤坏死因子-α(Tumor necrosis factor,TNF-α)、白介素-1β(Interleukin,IL)-1β和IL-6水平(P<0.05)。结论 rhPGRN通过显著上调PGRN来抑制海马小胶质细胞活化,随后抑制TNF-α-TNFR信号通路,最终影响炎症因子的释放,改善了S-DEP诱导的焦虑样行为。

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备注/Memo

备注/Memo:
基金项目:河南省卫生健康委员会科研项目(20240215)
更新日期/Last Update: 2025-04-20