[1]田丹丹,杨 阳.电针调控CASP-1/GSDMD细胞焦亡信号通路对抑郁症小鼠干预机制[J].陕西中医,2022,(7):851-856.[doi:DOI:10.3969/j.issn.1000-7369.2022.07.008]
　TIAN Dandan,YANG Yang.The intervention mechanism of electroacupuncture on CASP-1/GSDMD pyroptosis signaling pathway in depressed mice[J].,2022,(7):851-856.[doi:DOI:10.3969/j.issn.1000-7369.2022.07.008]
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电针调控CASP-1/GSDMD细胞焦亡信号通路对抑郁症小鼠干预机制
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《陕西中医》[ISSN:1000-7369/CN:61-1281/TN]

卷:
期数:
2022年7期
页码:
851-856
栏目:
基础研究
出版日期:
2022-07-05

文章信息/Info

Title:
The intervention mechanism of electroacupuncture on CASP-1/GSDMD pyroptosis signaling pathway in depressed mice
作者:
田丹丹; 杨 阳
(西北妇女儿童医院中医科,陕西 西安 710061)
Author(s):
TIAN Dandan; YANG Yang
(Department of Traditional Chinese Medicine,Northwest Women and Children's Hospital,Xi'an 710061,China)
关键词:
抑郁症;  电针;  小胶质细胞;  细胞焦亡;  突触可塑性;  神经炎症
Keywords:
Depression;  Electroacupuncture;  Microglia;  Pyroptosis;  Synaptic plasticity;  Nerve inflammation
分类号:
R 749.99
DOI:
DOI:10.3969/j.issn.1000-7369.2022.07.008
文献标志码:
A
摘要:
目的:观察电针干预对抑郁症模型小鼠行为学、CASP-1/GSDMD细胞焦亡信号通路相关蛋白及海马突触可塑性的影响,探讨早期电针干预抑郁症的效应及其机制。方法:健康C57BL/6小鼠随机分成四组:空白组、模型组、氟西汀、电针组,每组8只。除空白组外,其余各组均腹腔注射利血平构建急性抑郁小鼠模型。电针组取百会、内关给予电针干预,每次20 min,1次/d,连续7 d。通过悬尾实验、强迫游泳实验对各组小鼠进行行为学评价,蛋白印迹法(Western blot)、高尔基染色(Golgi-Cox staining)、免疫荧光(IF)法检测各组小鼠海马CASP-1/GSDMD细胞焦亡信号通路相关蛋白及海马突触可塑性的变化。结果:与空白组相比,模型组小鼠悬尾和强迫游泳实验中不动时间明显增加(P<0.001),小鼠海马CA1区树突棘密度显著减少(P<0.001),小鼠海马组织中CASP-1/GSDMD信号通路相关蛋白NLRP3、CASP-1、IL-1β表达水平显著增加(P<0.001),小鼠海马区小胶质细胞标志物Iba-1表达显著增加(P<0.001)。与模型组比较,电针组小鼠悬尾和强迫游泳实验中不动时间明显缩短(P<0.001),小鼠海马CA1 区树突棘密度明显增加(P<0.001),小鼠海马组织中CASP-1/GSDMD信号通路相关蛋白NLRP3、CASP-1、IL-1β表达水平显著下降(P<0.001),小鼠海马区小胶质细胞标志物Iba-1表达显著减少(P<0.001)。结论:电针干预可缓解利血平诱导的抑郁样行为,其机制可能与电针干预抑制CASP-1/GSDMD细胞焦亡信号通路及改善突触可塑性有关。
Abstract:
Objective:To observe the effects of electroacupuncture intervention on the behavior of depression model mice,the proteins related to the pyroptosis pathway of CASP-1/GSDMD and the plasticity of hippocampal synapses,and to explore the effects of early electroacupuncture intervention on depression and its mechanism.Methods:Healthy C57BL/6 mice were randomly divided into four groups:control,model,fluoxetine group and electroacupuncture group,with 8 mice in each group.Except control group,reserpine was injected intraperitoneally to establish acute depression mouse model.In the electroacupuncture group,“Baihui” and “Neiguan” were given electroacupuncture intervention,20 min each time,for consecutive 7 days.The tail suspension test,forced swimming test were used to evaluate the behavior of mice in each group.Western blot,Golgi-Cox staining,immunofluorescence staining method was used to detect the changes of proteins related to the signaling pathway of CASP-1/GSDMD pyroptosis and the synaptic plasticity of hippocampus.Results:Compared with control group,immobility time in tail suspension and forced swimming was significantly increased in model group(P<0.001),the density of dendritic spines in hippocampal CA1 region of mice was significantly decreased(P<0.001),the expression levels of CASP-1/GSDMD signaling pathway related proteins NLRP3,CASP-1,IL-1β in mouse hippocampus were significantly increased(P<0.001),the expression of microglial marker Iba-1 in the hippocampus of mice was significantly increased(P<0.001).Compared with the model group,the immobility time of the electroacupuncture group was significantly shorter in tail suspension and forced swimming(P<0.001),the density of dendritic spines in hippocampal CA1 region was significantly increased(P<0.001),the expression levels of CASP-1/GSDMD signaling pathway related proteins NLRP3,CASP-1,IL-1β in mouse hippocampus were significantly decreased(P<0.001),the expression of microglial marker Iba-1 in the hippocampus of mice was significantly decreased(P<0.001).Conclusion:Electroacupuncture intervention can alleviate depression-like behavior induced by reserpine,and the mechanism may be related to the inhibition of CASP-1/GSDMD pyroptosis signaling pathway and the improvement of synaptic plasticity.

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备注/Memo

备注/Memo:
基金项目:陕西省自然科学基金资助项目(2020JQ-464)
更新日期/Last Update: 2022-07-07