唑吡坦对慢性睡眠剥夺老年失眠大鼠神经递质及下丘脑-垂体-肾上腺皮质轴相关激素的影响  

Effects of zolpidem on neurotransmitters and hypothalamus-pituitary-adrenal cortex axis-related hormones in elderly rats with chronic sleep deprivation and insomnia

作　　者：林明霞[1] 李宝梅[1] 朱春燕[1] LIN Mingxia;LI Baomei;ZHU Chunyan(Department of Geriatrics,Hangzhou Seventh People's Hospital,Hangzhou 310063,China)

机构地区：[1]杭州市第七人民医院老年科,310063

出　　处：《浙江医学》2022年第12期1255-1260,共6页Zhejiang Medical Journal

摘　　要：目的探究唑吡坦对慢性睡眠剥夺老年失眠大鼠神经递质及下丘脑-垂体-肾上腺皮质轴(HPA)相关激素的影响。方法将60只32周龄SD大鼠随机分为环境对照组、模型组、唑吡坦低、中、高剂量组(0.52、1.05、2.10 mg/kg)和阳性药组(艾司唑仑0.50 mg/kg)。除环境对照组外,其余大鼠均建立慢性睡眠剥夺失眠模型,干预14 d并记录大鼠体质量变化和睡眠状况,比较大鼠脑系数;旷场实验和Morris水迷宫实验测试大鼠行为学变化,ELISA法检测下丘脑神经递质[多巴胺(DA)、5-羟色胺(5-HT)、去甲肾上腺素(NE)]水平以及血清下HPA相关激素[肾上腺皮质激素释放激素(CRH)、促肾上腺皮质激素(ACTH)、皮质酮(CORT)]水平,Western blot法检测大鼠下丘脑A型γ-氨基丁酸受体(GABAAR)、5-HT1A受体(5-HT1AR)蛋白表达水平。结果环境对照组大鼠体质量呈逐渐升高趋势,其余各组呈先降低后升高趋势,治疗后唑吡坦中、高剂量和阳性药组大鼠体质量均高于模型组(均P<0.05)。与环境对照组比较,模型组大鼠脑系数降低(P<0.05),5 min内运动距离和中央运动时间升高(P<0.05),90 s内逃避潜伏期延长(P<0.05),原平台象限停留次数、停留时间减少(P<0.05),血清CRH、ACTH、CORT水平升高(P<0.05),下丘脑DA、NE水平升高(P<0.05),5-HT水平降低(P<0.05),GABAAR、5-HT1AR蛋白相对表达水平降低(P<0.05);与模型组比较,唑吡坦中、高剂量和阳性药组大鼠脑系数升高(均P<0.05),5 min内运动距离和中央运动时间降低(P<0.05),90 s内逃避潜伏期缩短(P<0.05),原平台象限停留次数、停留时间增加(P<0.05),血清CRH、ACTH、CORT水平降低(P<0.05),下丘脑DA、NE水平降低(P<0.05),5-HT水平升高(P<0.05),GABAAR、5-HT1AR蛋白相对表达水平升高(P<0.05)。结论唑吡坦可提高老年慢性睡眠剥夺失眠大鼠学习和记忆能力,改善睡眠,与调节下丘脑神经递质紊乱和血清HPA相关激素水平相关。Objective To explore the effects of zolpidem on neurotransmitters and hypothalamus-pituitary-adrenal cortex axis(HPA)-related hormones in elderly rats with chronic sleep deprivation and insomnia.Methods Sixty 32-week old Sprague Dawley(SD)rats were randomly divided into control group,model group,low-,middle-and high-dose zolpidem groups(0.52,1.05,2.10 mg/kg)and positive drug group(0.50 mg/kg of estazolam).Except for the control group,the chronic sleep deprivation insomnia model was established,and the animals were intervened for 14 d;the changes in body mass and sleep status were recorded and the brain coefficient was compared.Open field test and Morris water maze were used to test the behavioral changes of rats.The contents of hypothalamic neurotransmitters dopamine(DA),5-hydroxytryptamine(5-HT),and norepinephrine(NE)]were detected with kits;the levels of serum HPA-related hormones corticotropinreleasing hormone(CRH),adrenocorticotropic hormone(ACTH)and cortisol(CORT)were detected with ELISA.Western blot was adopted to detect the protein expression levels of hypothalamicγ-aminobutyric acid type A receptor(GABAAR),5-HT1A receptor(5-HT1AR).Results The body mass of the rats in the control group showed a gradually increasing trend(P<0.05),while the body mass in the other groups showed a trend of decreasing first and then increasing(P<0.05),and the body mass in the middle-dose and high-dose zolpidem groups and positive drug group after treatment was heavier than that in the model group(P<0.05).Compared with the control group,the brain coefficient of rats in the model group was decreased(P<0.05),and the movement distance within 5 min and central movement time were shortened(P<0.05)while the escape latency within 90 s was prolonged(P<0.05),the number of stay in original platform quadrant and the stay time were decreased or shortened(P<0.05),and the levels of serum CRH,ACTH and CORT were enhanced(P<0.05),the contents of DA and NE in the hypothalamus were risen(P<0.05)while the content of 5-HT was reduced(P<0.05),and th

关 键 词：老年 失眠 唑吡坦 神经递质 下丘脑-垂体-肾上腺皮质轴 

分 类 号：R740[医药卫生—神经病学与精神病学]