引用本文:宋凯1,张虹2.电针调控杏仁核神经信号通路对创伤后应激障碍大鼠恐惧消退的影响[J].世界中医药,2024,(23):. |
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电针调控杏仁核神经信号通路对创伤后应激障碍大鼠恐惧消退的影响 |
Effect of Electroacupuncture Regulation of Neuronal Signaling Pathway in Amygdala on Fear Extinction in Post-traumatic Stress Disorder Rats |
投稿时间:2024-04-08 |
DOI:10.3969/j.issn.1673-7202.2024.23.006 |
中文关键词: 创伤后应激障碍 恐惧记忆 杏仁核 电针 杏仁核含WW结构域的E3泛素蛋白连接酶2(WWP2)/抑癌基因磷酸酶和张力蛋白同源蛋白(PTEN)/蛋白激酶B(AKT)信号通路 突触可塑性 突触可塑性蛋白突触素 生长相关蛋白-43 |
English Keywords:Post-traumatic stress disorder Fear memory Amygdala Electropuncture WWP2/PTEN/AKT pathway Synaptic plasticity Synaptophysin GAP-43 |
基金项目:国家自然科学基金项目(81873384);四川省自然科学基金资助项目(23NSFSC1821) |
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中文摘要: |
目的:探究电针对创伤后应激障碍(PTSD)大鼠恐惧消退的干预作用,以及对杏仁核含WW结构域的E3泛素蛋白连接酶2(WWP2)/抑癌基因磷酸酶和张力蛋白同源蛋白(PTEN)/蛋白激酶B(AKT)信号通路关键蛋白及突触可塑性蛋白突触素(SYN)、生长相关蛋白-43(GAP-43)表达的影响。方法:雄性斯泼累格·多雷(SD)大鼠被随机分为空白组、模型组、电针组,每组8只。采用增强的连续单一应激法构建PTSD模型,随后电针治疗21 d,通过旷场实验、场景化条件化恐惧反应实验、蛋白免疫印迹实验、免疫共沉淀实验、免疫组织化学实验评价电针的干预效应。结果:与空白组比较,模型组大鼠活动距离、穿越中央格数量及直立次数均少(P<0.05),造模成功;与模型组比较,电针组大鼠上述指标均改善(P<0.05)。与模型组比较,电针组大鼠在恐惧消退训练期和恐惧重建检测阶段大鼠的僵直时间百分比低(P<0.05)。与空白组比较,模型组大鼠杏仁核WWP2、磷酸化AKT蛋白表达低(P<0.05),PTEN蛋白表达高(P<0.05)。电针组上述蛋白表达变化逆转(P<0.05),PTEN与WWP2的结合能力上升。与空白组比较,模型组大鼠杏仁核组织中SYN、GAP-43蛋白阳性表达低(P<0.05),电针组杏仁核组织中SYN、GAP-43蛋白阳性表达高(P<0.05)。结论:电针可有效改善PTSD大鼠的自主活动和探索行为,促进恐惧记忆的消退,以上作用与杏仁核WWP2/PTEN/AKT信号通路的调控及突触可塑性有关。 |
English Summary: |
To investigate the intervention effect of electroacupuncture on fear extinction in rats with post-traumatic stress disorder(PTSD),and its impact on key proteins of the amygdala related to the WW domain-containing E3 ubiquitin protein ligase 2(WWP2)/tumor suppressor phosphatase and tensin homolog(PTEN)/protein kinase B(AKT) signaling pathway,as well as synaptic plasticity proteins synaptophysin(SYN) and growth-associated protein-43(GAP-43).Methods:Male Sprague-Dawley(SD) rats were randomly divided into the blank group,model group,and electroacupuncture group,with 8 rats in each group.PTSD was induced using the enhanced continuous single stress method,followed by electroacupuncture treatment for 21 days.The intervention effect was evaluated using open field test,contextual conditioned fear response experiment,Western blot,co-immunoprecipitation,and immunohistochemistry.Results:Compared to the blank group,the model group exhibited reduced activity distance,fewer central crossings,and fewer standing counts(P<0.05),confirming successful modeling.Compared to the model group,the electroacupuncture group showed significant improvement in these indicators(P<0.05).During the fear extinction training and fear reinstatement testing phases,the electroacupuncture group exhibited a lower percentage of freezing time than the model group(P<0.05).In the amygdala,the expression of WWP2 and phosphorylated AKT proteins was lower in the model group than that in the blank group(P<0.05),while PTEN protein expression was higher(P<0.05).These protein expression changes were reversed in the electroacupuncture group(P<0.05),with an increased binding ability of PTEN to WWP2.Additionally,compared to the blank group,the expression of SYN and GAP-43 proteins in the amygdala was lower in the model group(P<0.05),while it was higher in the electroacupuncture group(P<0.05).Conclusion:Electroacupuncture effectively improves autonomous activity and exploratory behavior in PTSD rats,promotes the extinction of fear memory,and these effects are related to the regulation of the WWP2/PTEN/AKT signaling pathway in the amygdala and synaptic plasticity. |
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