木犀草素调节Nrf2/HO-1/NLRP3信号通路对抑郁症小鼠海马神经元凋亡的影响  

The Impacts of Iuteolin on Hippocampal Neuronal Apoptosis in Depressed Mice by Regulating the Nrf2/HO-1/NLRP3 Signaling Pathway

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作  者:杨沫迪 翟亮 王艳玲 薛斌 刘青霞 田红梅 张金慧 YANG Modi;ZHAI Liang;WANG Yanling;XUE Bin;LIU Qingxia;TIAN Hongmei;ZHANG Jinhui(Department of Psychiatry,the First Psychiatric Hospital of Harbin,Harbin 150056,China)

机构地区:[1]哈尔滨市第一专科医院精神科,哈尔滨150056

出  处:《中国细胞生物学学报》2025年第2期221-228,共8页Chinese Journal of Cell Biology

基  金:黑龙江省卫生计生委科研课题(批准号:2018-159)资助的课题。

摘  要:该研究主要探讨木犀草素(Luteolin)对抑郁症小鼠海马神经元凋亡及核因子E2相关因子2/血红素加氧酶1/Nod样受体蛋白3(Nrf2/HO-1/NLRP3)信号通路的影响。该研究先构建抑郁症小鼠模型,将造模成功小鼠随机分为模型组(Model组),木犀草素低、高剂量组(Luteolin-L、Luteolin-H组),木犀草素高剂量+Nrf2抑制剂组(Luteolin-H+ML385组),另取正常健康小鼠作为对照组(Control组);然后对所有小鼠进行抑郁样行为检测;ELISA检测海马组织炎症及氧化应激水平;HE染色检测海马组织CA3区病理损伤情况;TUNEL染色检测神经元凋亡情况;Western blot检测Nrf2/HO-1/NLRP3信号通路及凋亡相关蛋白表达情况。结果表明,Model组较Control组海马组织结构受损,神经元出现神经元性脓疱变性,排列松散,核固缩深染,部分核碎片化,核仁模糊甚至消失,糖水偏好指数、SOD、GSH水平及Bcl-2、Nrf2、HO-1表达水平降低;强迫游泳静止时间,TNF-α、IL-6、IL-β、MDA水平及神经元凋亡率、Bax、NLRP3表达水平升高(P<0.05);木犀草素处理可改善海马组织病理损伤,升高糖水偏好指数、SOD、GSH水平及Bcl-2、Nrf2、HO-1表达水平,降低强迫游泳静止时间、TNF-α、IL-6、IL-β、MDA水平及神经元凋亡率、Bax、NLRP3表达水平(P<0.05);Nrf2抑制剂ML385处理可部分减弱木犀草素对抑郁症小鼠海马神经元凋亡的改善作用。总之,木犀草素可抑制抑郁症小鼠海马神经元凋亡,其作用机制与激活Nrf2/HO-1/NLRP3信号通路相关。The aim of this study was to investigate the impacts of Luteolin on hippocampal neuronal apoptosis and Nrf2/HO-1/NLRP3(nuclear factor-erythroid 2-related factor 2/heme oxygenase 1/NOD-like receptor thermal protein domain associated protein 3)signaling pathway in mice with depression.In this study,a depression mouse model was constructed,and successfully modeled mice were randomly assigned into a model group,Luteolin-L and Luteolin-H groups,and Luteolin-H+ML385 group(Luteolin-high dose+Nrf2 inhibitor group).Normal healthy mice were also selected as the control group.Then all mice were tested for depression like behavior.ELISA was applied to detect inflammation and oxidative stress levels in hippocampal tissue.HE staining was applied to detect pathological damage in CA3 region of hippocampal tissue.TUNEL staining was applied to detect neuronal apoptosis.Western blot was applied to detect the Nrf2/HO-1/NLRP3 signaling pathway and the expression of apoptosis related proteins.The results showed that compared with the control group,the hippocampal tissue structure in the model group was damaged,neuronal pustular degeneration of neurons appeared,with loose array,hyperchromia of nuclei,partial nucleus fragmentation,blurred or even disappeared nucleolus,and the sugar and water preference index,SOD and GSH levels and the expression of Bcl-2,Nrf2 and HO-1 were decreased.Static time,TNF-α,IL-6,IL-β,MDA levels,neuronal apoptosis rate,Bax,NLRP3 expression were increased(P<0.05).Luteolin treatment could improve the pathological injury of hippocampal tissue,increase the sugar water preference index,SOD,GSH levels and the expressions of Bcl-2,Nrf2 and HO-1,decrease the resting time of forced swimming,TNF-α,IL-6,IL-β,MDA levels,neuronal apoptosis rate,Bax and NLRP3 expression(P<0.05).Treatment with ML385,an Nrf2inhibitor,partially attenuates the effect of luteolin on hippocampal neuron apoptosis in depressed mice.In conclusion,Luteolin can alleviate hippocampal neuronal apoptosis in mice with depression,and its mechanism of ac

关 键 词:木犀草素 核因子E2相关因子2/血红素加氧酶1/Nod样受体蛋白3信号通路 抑郁症 海马神经元 凋亡 

分 类 号:R285.5[医药卫生—中药学]

 

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