医学分子生物学杂志 ›› 2025, Vol. 22 ›› Issue (1): 55-61.doi: 10.3870/j.issn.1672-8009.2025.01.009

• 论著 • 上一篇    下一篇

基于 PI3K / AKT 信号通路探讨 DJ-1 蛋白对抑郁症大鼠海马中神经递质的影响 #br#

  

  1. 泰州市第四人民医院药学部 江苏省泰州市, 225300
  • 出版日期:2025-01-31 发布日期:2025-02-28
  • 基金资助:
    泰州市凤城英才青年人才托举工程资助项目, 泰州市海陵区科技发展计划 (社会发展) 项目

Effect of DJ-1 Protein Expression on Neurotransmitters Levels in Hippocampus of Depression Rats via PI3K / AKT Signaling Pathway #br#

  1. Department of Pharmacy, Taizhou Fourth Peoples Hospital, Taizhou, Jiangsu, 225300, China
  • Online:2025-01-31 Published:2025-02-28

摘要: 目的 探讨 DJ-1 蛋白对抑郁症大鼠神经递质的影响方法 TUNEL ( terminal deoxynucleotidyltransferase-mediated dUTP nick-end labeling) 试剂盒检测细胞凋亡率酶联免疫吸附法测定血清中肿瘤坏死因子-α (tumor necrosis factor-α, TNF-α) 和白细胞介素-6 ( interleukin-6, IL-6) 的含量, 海马区中 5-羟色胺 (5-hydroxytryptamine, 5-HT)、 5-羟吲哚乙酸 (5-hydroxyindoleacetic acid, 5-HIAA)、 多巴胺 ( dopamine, DA) 的水平; 蛋白质印迹检测海马区 DJ-1、 磷脂酰肌醇 3 激酶 (phosphatidylinositol 3 kinase, PI3K)、 蛋白激酶 B (protein kinase B, AKT)、 p-PI3K、 p-AKT、 Bcl-2 Bcl-2 相关 X 蛋白 ( Bcl-2 associated X protein, Bax) 的表达结果 过表达 DJ-1 后能明显降低中细胞凋亡率和血清中 TNF-α IL-6 的含量, 上调海马区5-HT、 5-HIAA、 DA 的水平, 上调 p-PI3K、 p-AKT Bcl-2 的表达, 抑制 Bax 的表达, PI3K 抑制剂LY294002 可部分解除过表达 DJ-1 对神经元细胞的保护作用结论 过表达 DJ-1 后能明显抑制抑郁症大鼠炎症性应激, 降低细胞的凋亡率, 上调中 5-HT、 5-HIAA DA 的含量, 这可能与激活 PI3K / AKT 信号有关

关键词: DJ-1 蛋白, 抑郁症, 神经递质, 磷脂酰肌醇 3 激酶/ 蛋白激酶 B 信号

Abstract: Objective To investigate the effect of DJ-1 protein expression on neurotransmitters levels in the hippocampus of depression rats. Methods Terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) was used to detect the apoptosis in hippocampus. Enzyme linked immunosorbent assay was used to determine the levels of tumor necrosis factor-α ( TNF-α) and interleukin 6 (IL-6) in serum, and the levels of 5-hydroxytryptamine (5-HT), 5-hydroxyindoleacetic acid (5-HIAA) and dopamine (DA) in hippocampus. Western blotting assay was used to detect the expression levels of DJ-1, PI3K, AKT, phosphorylated PI3K (p-PI3K), phosphorylated AKT ( p-AKT), Bcl-2 and Bcl-2 associated X protein ( Bax) in the hippocampus ofrats. Results Overexpression of DJ-1 significantly reduced the cell apoptosis rate in hippocampusand the levels of TNF-α and IL-6 in serum and the expression level of Bax in hippocampus, and upregulated the levels of 5-HT, 5-HIAA and DA in hippocampus and the expression levels of p-PI3K, p-AKT and Bcl-2 in hippocampus. However, the PI3K inhibitor LY294002 could partially reversethe protective effect of DJ-1 overexpression on neurons. Conclusion Overexpression of DJ-1 couldsignificantly inhibit inflammatory stress in the hippocampus of depression rats, reduce the apoptosis rate of neurons in the hippocampus, upregulate the levels of 5-HT, 5-HIAA and DA in the hippocampus, the mechanism may be related to the activation of PI3K / AKT signaling pathway.

Key words:

DJ-1, depression, neurotransmitters, phosphatidylinositol 3 kinase / protein kinase B signaling pathway

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