半夏秫米汤对失眠大鼠下丘脑5-HT介导的cAMP/CREB/BDNF通路的影响  

Effects of Banxia Shumi(半夏秫米)Decoction on Hypothalamic 5-HT-Mediated c AMP/CREB/BDNF Pathway in Insomniac Rats

作　　者：陈燕[1] 许晓丽 陈亚萍 张玉琴[1] 曹亚俊 陈婷 刘玉凤 黄枚[1] 南丽红[1] CHEN Yan;XU Xiaoli;CHEN Yaping;ZHANG Yuqin;CAO Yajun;CHEN Ting;LIU Yufeng;HUANG Mei;NAN Lihong(College of Pharmacy,Fujian University of Traditional Chinese Medicine,Fuzhou 350122;Xiamen Fifth Hospital,Xiamen 361101;Fuzhou Traditional Chinese Medicine Hospital,Fuzhou 350001)

机构地区：[1]福建中医药大学药学院,福州350122 [2]厦门市第五医院,厦门361101 [3]福州市中医院,福州350001

出　　处：《中药药理与临床》2024年第10期10-14,共5页Pharmacology and Clinics of Chinese Materia Medica

基　　金：福建省自然科学基金项目(编号:2021J01926);福建省卫健委福建省中医药科技项目(编号:2021zyyj67);福建省卫健委青年科研课题(编号:2020QNA075)。

摘　　要：目的:探讨半夏秫米汤对失眠模型大鼠的行为学和下丘脑5-羟色胺(5-HT)介导环磷酸腺苷(cAMP)/cAMP应答元件结合蛋白(CREB)/脑源性神经营养因子(BDNF)通路的影响。方法:SD大鼠随机分为正常对照组、模型对照组、半夏秫米汤8.1、16.2、32.4 g/kg组、地西泮0.9 mg/kg组。除正常对照组外,其余大鼠采用对氯苯丙氨酸(PCPA)建立失眠模型。各组大鼠灌服相应药物或蒸馏水7 d后,采用戊巴比妥钠睡眠试验、旷场试验、Morris水迷宫试验检测行为学;ELISA法检测下丘脑5-HT、腺苷酸环化酶(AC)、cAMP含量;Western blot法检测下丘脑5-羟色胺1A受体(5-HT_(1A)R)、5-羟色胺2A受体(5-HT_(2A)R)、蛋白激酶A(PKA)、p-CREB、CREB、BDNF蛋白表达。结果:与正常对照组相比,模型对照组大鼠睡眠潜伏期、静止时间和粪便粒数、水迷宫游泳总路程及逃避潜伏期显著增加(P<0.01),睡眠持续时间、平均速度、中央格跨格次数、总活动距离、目标象限穿越次数和停留时间显著减少(P<0.01),下丘脑5-HT、AC、cAMP含量显著降低,下丘脑5-HT_(1A)R、PKA、p-CREB和BDNF蛋白表达显著下调(P<0.01);相较于模型对照组,半夏秫米汤组大鼠睡眠潜伏期、静止时间、粪便粒数、逃避潜伏期、游泳总路程明显减少(P<0.05或P<0.01),睡眠持续时间、平均速度、中央格跨格次数、总活动距离、目标象限穿越次数和停留时间明显增加,5-HT、AC及cAMP含量升高,5-HT_(1A)R及PKA、p-CREB和BDNF蛋白表达明显上调(P<0.05或P<0.01)。结论:半夏秫米汤可通过激活下丘脑5-HT及1A受体介导的cAMP/CREB/BDNF通路,改善失眠大鼠的睡眠并减少焦虑情绪,提升学习记忆能力。Objective:To investigate the effects of Banxia Shumi(半夏秫米)Decoction on the behavior and hypothalamic 5-hydroxytryptamine(5-HT)-mediated cyclic adenosine monophosphate(cAMP)/cAMP response element-binding protein(CREB)/brain-derived neurotrophic factor(BDNF)pathway in insomnia model rats.Methods:SD rats were randomly divided into a normal control group,a model control group,Banxia Shumi Decoction groups(8.1,16.2,32.4 g/kg),and a diazepam group(0.9 mg/kg).Except for the normal control group,all rats were treated with para-chlorophenylalanine(PCPA)to establish an insomnia model.After 7 days of oral administration of corresponding drugs or distilled water,behavior tests,including the pentobarbital sodium sleep test,open field test,and Morris water maze test,were performed.Enzyme-linked immunosorbent assay(ELISA)was used to detect the levels of 5-HT,adenylate cyclase(AC),and cAMP in the hypothalamus.Western blot was used to measure the protein expression of hypothalamic 5-HT_(1A)R,5-HT_(2A)R,protein kinase A(PKA),p-cAMP response element-binding protein(p-CREB),CREB,and brain-derived neurotrophic factor(BDNF).Results:Compared with the normal control group,the model control group showed significant increases in sleep latency,immobility time,fecal pellet count,total swimming distance,and escape latency in the water maze,while the sleep duration,average speed,central grid crossings,total activity distance,target quadrant crossings,and time spent in the target quadrant were significantly decreased.The levels of 5-HT,AC,and cAMP in the model control group were significantly reduced,and the protein expressions of 5-HT_(1A)R,PKA,p-CREB,and BDNF were significantly downregulated(P<0.01).Compared with the model control group,the Banxia Shumi Decoction groups significantly reduced sleep latency,immobility time,fecal pellet count,escape latency,and total swimming distance,while increasing sleep duration,average speed,central grid crossings,total activity distance,target quadrant crossings,and time spent in the target quadra

关 键 词：半夏秫米汤 失眠 下丘脑 5-羟色胺 环磷酸腺苷/环磷酸腺苷应答元件结合蛋白/脑源性神经营养因子通路 

分 类 号：R285.5[医药卫生—中药学]