酸枣仁皂苷对失眠模型大鼠的干预作用及对cAMP/CREB/BDNF和PI3K/Akt通路的影响  

Ameliorating effect of jujuboside on insomnia model rats and its effect on cAMP/CREB/BDNF and PI3K/Akt pathways

作　　者：袁健华 顾鸣鸣 袁育红 YUAN Jian-hua;GU Ming-ming;YUAN Yu-hong(Department of Respiratory and Critical Care Medicine,Haimen District People's Hospital,Nantong 226199;Department of Cardiothoracic Surgery,Affiliated Hospital of Nantong University,Nantong 226006;Department of Traditional Chinese Medicine,Haimen District People's Hospital,Nantong 226199,China)

机构地区：[1]南通市海门区人民医院呼吸与危重症医学科,江苏南通226199 [2]南通大学附属医院心胸外科,江苏南通226006 [3]南通市海门区人民医院中医科,江苏南通226199

出　　处：《解剖科学进展》2024年第3期229-232,共4页Progress of Anatomical Sciences

基　　金：2023年南通市妇幼健康专科联盟科研课题(TFM202308)。

摘　　要：目的基于环磷酸腺苷/cAMP应答元件结合蛋白/脑源性神经营养因子(cAMP/CREB/BDNF)和磷脂酰肌醇-3-羟激酶/蛋白激酶B(PI3K/Akt)信号通路探讨酸枣仁皂苷改善大鼠睡眠的作用机制。方法将SD大鼠随机分为空白对照组、模型、酸枣仁皂苷低、高剂量组。采用对氯苯丙氨酸(PCPA)诱导大鼠睡眠障碍;观察各组大鼠一般状态;采用动物睡眠生物解析系统记录脑电图(EEG)和肌电图(EMG)信号,分析大鼠夜晚和白天觉醒(Wake)总量和非快速眼动(NREM)睡眠、快速眼动(REM)睡眠总量;ELISA检测下丘脑5-羟色胺(5-HT)、多巴胺(DA)及环磷酸腺苷(cAMP)含量;Western blot法检测下丘脑环磷腺苷效应元件结合蛋白(CREB)、磷酸化CREB(p-CREB)、脑源性神经营养因子(BDNF)、磷脂酰肌醇-3-羟激酶(PI3K)、蛋白激酶B(Akt)及p-Akt蛋白表达。结果酸枣仁皂苷干预后,大鼠精神状态明显改善,NREM睡眠和REM睡眠总量显著增加,Wake总量显著减少,下丘脑5-HT、cAMP含量显著增加,DA含量显著降低,BDNF、p-CREB、PI3K及p-Akt蛋白表达水平均显著升高。结论酸枣仁皂苷对PCPA所致大鼠睡眠障碍具有一定的改善作用,其作用机制可能与激活cAMP/CREB/BDNF和PI3K/Akt信号通路有关。Objective To explore the mechanism of jujuboside improving sleep in rats based on cAMP/CREB/BDNF and PI3K/Akt signaling pathways.Methods SD rats were randomly divided into blank control group,model group,jujuboside low dose group and high dose group.Sleep disorders were induced by p-chlorophenylalanine(PCPA).The general state of rats in each group was observed.Electroencephalogram(EEG)and electromyogram(EMG)signals were recorded by animal sleep bioanalytic system,and the total amount of Wake,non-rapid eye movement(NREM)and rapid eye movement(REM)sleep at night and day were analyzed.The contents of 5-hydroxytryptamine(5-HT),dopamine(DA)and cyclic adenosine phosphate(cAMP)were detected by ELISA.The expressions of cyclic adenosine phosphatide effer-binding protein(CREB),phosphorylated CREB(p-CREB),brain-derived neurotrophic factor(BDNF),phosphatidylinositol-3-hydroxykinase(PI3K),protein kinase B(Akt)and p-Akt protein in hypothalamus were detected by Western blot.Results After the intervention of jujuboside,the mental state of rats was significantly improved,the total amount of NREM sleep and REM sleep was significantly increased,the total amount of Wake was significantly decreased,the content of 5-HT and cAMP in hypothalamus was significantly increased,the content of DA was significantly decreased,and the expression levels of BDNF,p-CREB,PI3K and p-Akt were significantly increased.Conclusion Jujuboside has a certain effect on PCPA-induced sleep disorder in rats,and its mechanism of action may be related to the activation of cAMP/CREB/BDNF and PI3K/Akt signaling pathways.

关 键 词：失眠 酸枣仁皂苷 cAMP/CREB/BDNF信号通路 PI3K/Akt信号通路 

分 类 号：R749.7[医药卫生—神经病学与精神病学]