[1]郭鑫,汪盛,周德喜,等.拉喹莫德改善神经炎症中突触可塑性的作用研究[J].卒中与神经疾病杂志,2024,31(01):36-41.[doi:10.3969/j.issn.1007-0478.2024.01.007]
　Guo Xin,Wang Sheng,Zhou Dexi,et al.Effect of Laquimod on Synaptic plasticity in Neuroinflammation[J].Stroke and Nervous Diseases,2024,31(01):36-41.[doi:10.3969/j.issn.1007-0478.2024.01.007]
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拉喹莫德改善神经炎症中突触可塑性的作用研究()
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《卒中与神经疾病》杂志[ISSN:1007-0478/CN:42-1402/R]

卷:
第31卷
期数:
2024年01期
页码:
36-41
栏目:
论著
出版日期:
2024-02-20

文章信息/Info

Title:
Effect of Laquimod on Synaptic plasticity in Neuroinflammation
文章编号:
1007-0478(2024)01-0036-06
作者:
郭鑫; 汪盛; 周德喜; 栾家杰
241001 安徽省芜湖市皖南医学院第一附属医院（弋矶山医院）临床药学科\[郭鑫 汪盛 周德喜 栾家杰（通信作者）\]
Author(s):
Guo Xin;  Wang Sheng;  Zhou Dexi;  et al.
Clinical Pharmacy Department, the First Affiliated Hospital of Wannan Medical College, Wuhu Anhui 241001
关键词:
拉喹莫德; 神经炎症; 神经元; 突触结构可塑性
Keywords:
Laquinimod Neuroinflammation Neurons Synaptic structural plasticity
分类号:
R743.3
DOI:
10.3969/j.issn.1007-0478.2024.01.007
文献标志码:
A
摘要:
目的 使用脂多糖(Lipopolysaccharide，LPS)诱导建立神经炎症模型研究拉喹莫德(Laquinimod，LAQ)对突触结构可塑性的改善作用。 方法 培养原代海马神经元、小胶质细胞株BV-2细胞，且分为对照\[磷酸缓冲盐溶液（Phosphate buffer saline，PBS）\]组（常规培养）、LPS组（低糖+5 μg/mL LPS刺激4 h、复糖2 h）、LAQ组（预给药100 nM/mL LAQ 2 h、低糖+5 μg/mL LPS刺激4 h、复糖+100 nM/mL LAQ 2 h）；免疫荧光检测神经生长相关蛋白-43(Growth-associated protein，GAP-43)、微管相关蛋白-2(Microtubule associated protein 2，MAP-2)、突触素（Synaptophysin，SYN）、突触后密度蛋白-95（Postsynaptic density protein 95，PSD-95）、白细胞介素10（Interleukin-10，IL-10）、肿瘤坏死因子α（Tumor necrosis factor alpha，TNF-α）蛋白分布；Western blot检测蛋白激酶（Protein kinase B，Akt）、磷酸化蛋白激酶(Phosphorylated protein kinase B，p-Akt)、核因子κB（Nuclear factor kappa-B，NF-κB）、磷酸化核因子κB (Phosphorylated nuclear factor kappa-B，p-NF-κB）、核因子ΚB抑制因子Α（Recombinant nuclear factor kb inhibitor A，IκBα）、磷酸化核因子ΚB抑制因子Α（Phosphorylated recombinant nuclear factor KB inhibitor A，p-IκBα）、β-肌动蛋白（Actin beta，β-actin）蛋白表达水平。 结果 与PBS组比较，LPS组BV-2细胞TNF-α表达水平增高、IL-10表达水平降低，细胞胞体增大，轴突缩回；Akt，NF-κB，IκBα蛋白磷酸化水平升高；SYN与PSD-95蛋白表达减少、分布不连贯，树突棘数量减少，神经元间连接减少；LAQ组BV-2细胞TNF-α表达水平降低、IL-10表达水平增高，轴突延伸，胞体体积变回正常，且降低了Akt，NF-κB，IκBα的磷酸化水平；神经元SYN，PSD-95蛋白表达水平增高且分布于各神经元突触连接处，树突棘数量增多，神经元间连接增多。 结论 LAQ潜在机制是通过抑制Akt-NF-κB通路来减轻神经炎症、抑制突触蛋白的丢失，保护了树突棘使得突触连接增多，对突触结构可塑性起到积极作用。
Abstract:
Objective〖WTBZ〗 The neuroinflammation indu ced by Lipopolysaccharide (LPS) was used to investigate the role of laquinimod (LAQ) on the plasticity of synaptic structure. 〖WTHZ〗Methods 〖WTBZ〗 The primary hippocampal neurons and Microglia cell line (BV-2 cells) were cultured, Divided into control (PBS) group (conventional culture), LPS group (low sugar+5 μg/mL LPS stimulation for 4 hours, normal sugar for 2 hours), LAQ group (pre-administration 100 nM/mL LAQ for 2 hours, normal sugar+5 μg/mL LPS stimulation for 4 hours, normal sugar+100 nM/mL LAQ for 2 hours). Immunofluorescence detection of GAP-43、MAP-2、Synaptophysin（SYN）、PSD-95、IL-10、TNF-α protein distribution. Western blot detection of Akt、p-Akt、NF-κB、p-NF-κB、IκBα、p-IκBα、β-actin protein expression. 〖WTHZ〗Results 〖WTBZ〗 Compared with the PBS group, the LPS group showed an increase of TNF-α and decrease of IL-10 in the BV-2 cell, cell body enlargement and axonal retraction; The level of p-Akt、p-NF-κB、p-IκBα protein increased; Synaptophysin (SYN) and PSD-95 protein expression reduced and inconsistent distribution, neuron number of dendritic spines reduced, resulting in reduced intercellular connections. LAQ group showeddecrease d TNF-α and increased IL-10 in the BV-2 cell, axon extension, cell volume returned to normal, the level of p-Akt、p-NF-κB、p-IκBα protein decreased; Synaptophysin (SYN) and PSD-95 protein increased and distributed at synaptic connections of various neurons, the number of dendritic spines also increased. 〖WTHZ〗Conclusion 〖WTBZ〗 LAQ plays a positive role in synaptic structural plasticity by inhibiting the Akt-NF-κB pathway, which reduces neuroinflammation，inhibits the loss of synaptic proteins and protects synaptic connections.

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备注/Memo

备注/Memo:
基金项目：国家自然科学基金（批号为822200662）
更新日期/Last Update: 2024-02-20