基础医学与临床2024，Vol.44Issue(8)：1126-1132,7.DOI:10.16352/j.issn.1001-6325.2024.08.1126
青蒿琥酯调节cGAS-STING信号通路对抑郁症模型小鼠神经炎性反应的影响
Effect of artesunate on neuroinflammation in depressed mouse model by regulating cGAS-STING signaling pathway
摘要
Abstract
Objective To investigate the effect of artesunate(ART)on neuroinflammation in depressed mice by regulating the cyclic guanosine monophosphate-adenosine monophosphate synthase(cGAS)-stimulator of interferon gene(STING)pathway.Methods Mice were divided into model group,control group,low-dose ART group,high-dose ART group,fluoxetine group,and high-dose ART+RocA(cGAS-STING pathway activator)group.Sugar solution consumption experiment and forced swimming experiment were applied to evaluate the depressive behavior of mice;HE staining microscopy was applied to detect pathological changes in hippocampal tissue;ELISA method was applied to detect the level of interleukin-6(IL-6),tumor necrosis factor-α(TNF-α),serotonin(5-HT)and dopa-mine(DA);TUNEL staining microscopy was applied to detect neuronal apoptosis;Western blot was applied to detect Bcl-2 associated X protein(Bax),p53,cGAS,and STING proteins.Results Compared to the control group,the mice in the model group exhibited neuronal pustule degeneration,the sugar water consumption rate,level of 5-HT and DA decreased,the rest time of forced swimming increased.The level of IL-6 and TNF-α,neuronal apoptosis rate,expression of Bax,p53,cGAS,and STING proteins all elevated(P＜0.05);Compared with model group,the damage to hippocampus neurons in the ART low-dose group,ART high-dose group and fluoxetine group neuronal pus-tular degeneration was alleviated,while sugar water consumption rate,5-HT,and DA levels increased,the rest time of forced swimming reduced,the level of IL-6 and TNF-α,neuronal apoptosis rate and the expression of Bax,p53,cGAS,and STING proteins reduced(P＜0.05);RocA reversed the improvement effect of high-dose ART on depression in mice.Conclusions ART inhibits neuroinflammation and neuronal apoptosis in depressed mice,and up-regulates amine neurotransmitters expression.The mechanism is potentially related to the blocking of cGAS-STING pathway.关键词
青蒿琥酯/环磷酸鸟苷-腺苷酸合成酶-干扰素基因刺激因子通路/抑郁症/炎性反应/凋亡Key words
artesunate/cyclic guanosine monophosphate-adenosine monophosphate synthase-stimulator of interferon gene pathway/depression/inflammation/apoptosis分类
医药卫生引用本文复制引用
高超,张润菡,王伟,赵曼婷,焦艳,李喆..青蒿琥酯调节cGAS-STING信号通路对抑郁症模型小鼠神经炎性反应的影响[J].基础医学与临床,2024,44(8):1126-1132,7.基金项目
沧州市重点研发计划指导项目(222106097) （222106097）
