首页|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

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

扫码查看
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 deoxynucleotidyl transferase-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 和 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和IL-6的含量,上调海马区5-HT、5-HIAA、DA的水平,上调p-PI3K、p-AKT和Bcl-2的表达,抑制Bax的表达,但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和DA的含量,这可能与激活PI3K/AKT信号有关.
Effect of DJ-1 Protein Expression on Neurotransmitters Levels in Hip-pocampus of Depression Rats via PI3K/AKT Signaling Pathway
Objective To investigate the effect of DJ-1 protein expression on neurotransmitters levels in the hippocampus of depression rats.Methods Terminal deoxynucleotidyl transferase-medi-ated 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-hydroxyin-doleacetic 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),phospho-rylated AKT(p-AKT),Bcl-2 and Bcl-2 associated X protein(Bax)in the hippocampus of rats.Results Overexpression of DJ-1 significantly reduced the cell apoptosis rate in hippocampus and the levels of TNF-α and IL-6 in serum and the expression level of Bax in hippocampus,and up-regulated 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 reverse the protective effect of DJ-1 overexpression on neurons.Conclusion Overexpression of DJ-1 could significantly 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 hippo-campus,the mechanism may be related to the activation of PI3K/AKT signaling pathway.

DJ-1depressionneurotransmittersphosphatidylinositol 3 kinase/protein ki-nase B signaling pathway

李笑然、蔡云峰、丁兆猛、孙祥生、卢煜晨

展开 >

泰州市第四人民医院药学部 江苏省泰州市,225300

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

2025

医学分子生物学杂志
华中科技大学同济医学院

医学分子生物学杂志

影响因子:0.311
ISSN:1672-8009
年,卷(期):2025.22(1)