龙牡桂枝汤对慢性应激状态下ADHD大鼠学习记忆及海马-HPA轴的影响  

Effects of Longmu Guizhi Decoction on learning and memory ability and hippocampal-HPA axis of ADHD rats with chronic stress

作　　者：唐彦 徐寅 张值伟 普芳 李竹琴 TANG Yan;XU Yin;ZHANG Zhiwei;PU Fang;LI Zhuqin(The First Clinical Medical College of Yunnan University of Chinese Medicine,Kunming 650500,China)

机构地区：[1]云南中医药大学第一临床医学院,昆明650500

出　　处：《中华中医药杂志》2024年第1期382-386,共5页China Journal of Traditional Chinese Medicine and Pharmacy

基　　金：国家自然科学基金项目(No.81760880,No.82260954)。

摘　　要：目的:观察龙牡桂枝汤对慢性应激状态下注意缺陷多动障碍(ADHD)模型大鼠学习记忆能力和海马-下丘脑-垂体-肾上腺轴(HPA轴)的影响。方法:32只ADHD模型动物幼年自发性高血压大鼠(SHR)随机分为空白组、慢性应激组、盐酸哌甲酯组和龙牡桂枝汤组,各8只。采用Morris水迷宫实验评价大鼠学习记忆能力,ELISA法检测血清促肾上腺皮质激素(ACTH)、皮质酮(CORT)、促肾上腺皮质释放激素(CRH)水平,RTPCR法检测下丘脑CRH、促肾上腺皮质激素释放激素受体1(CRHR1)、促肾上腺皮质释放激素结合蛋白(CRH-BP)及垂体CRHR1、CRH-BP mRNA表达水平,免疫组化法检测海马糖皮质激素受体(GR)、盐皮质激素受体(MR)蛋白表达水平。结果:与空白组比较,慢性应激组寻找平台的潜伏期显著延长(P<0.01),在目标象限停留时间及穿越平台数显著减少(P<0.05),血清CORT、CRH、ACTH水平显著升高(P<0.01,P<0.05),下丘脑CRH、CRHR1、CRH-BP mRNA及垂体CRHR1、CRH-BP mRNA表达升高(P<0.05);海马中GR表达下降、MR表达升高(P<0.05)。与慢性应激组比较,龙牡桂枝汤组和盐酸哌甲酯组寻找平台的时间减少(P<0.01),在目标象限停留的时间和穿越平台数增多(P<0.05),血清CORT、ACTH、CRH水平显著降低(P<0.01),下丘脑CRH、CRHR1、CRH-BP mRNA及垂体CRHR1、CRH-BP mRNA表达下降(P<0.05,P<0.01),海马中GR蛋白表达升高、MR蛋白表达下降(P<0.05,P<0.01)。结论:慢性应激可致ADHD的HPA轴功能亢进,学习记忆能力下降,龙牡桂枝汤可通过减少下丘脑CRH、CRHR1、CRH-BP mRNA及垂体CRHR1、CRH-BP mRNA表达,调控海马中GR和MR的表达,提高慢性应激状态下ADHD的学习记忆能力。Objective:To investigate the effects of Longmu Guizhi Decoction on learning and memory and hippocampalattention deficit hyperactivity disorder(HPA)axis with chronic stress in the hypothalamic-pituitary-adrenal(ADHD)model rats.Methods:A total of 32 Juvenile spontaneously hypertensive rats were randomly divided into blank group,chronic stress group,methylphenidate hydrochloride group and Longmu Guizhi Decoction group,with 8 rats in each group.The Morris water maze test was used to evaluate the learning and memory ability of rats.The levels of adrenocorticotropin hormone(ACTH),corticosterone(CORT)and corticotropin releasing hormone(CRH)in serum were detected by ELISA.The mRNA expressions of CRH,corticotropin releasing hormone receptor 1(CRHR1)and CRH binding protein(CRH-BP)in hypothalamus,CRHR1 and CRHBP in pituitary were detected by RT-PCR method.The protein expression of glucocorticoid receptor(GR)and mineralocorticoid receptor(MR)in hippocampus were detected by immunohistochemistry method.Results:Compared with the blank group,the incubation period for finding the platform in the model group was significantly longer(P<0.01),and the residence time in the target quadrant and the times of entering the platform quadrant were reduced(P<0.05).The levels of serum CORT,CRH and ACTH were significantly increased(P<0.01,P<0.05),the mRNA expressions of CRH,CRHR1,CRH-BP in the hypothalamus,CRHR1 and CRH-BP in the pituitary were increased(P<0.05),GR protein expression was decreased and MR protein expression was increased in hippocampus(P<0.05).Compared with the chronic stress group,the time to find the platform in Longmu Guizhi decoction group and the methylphenidate hydrochloride group were decreased(P<0.01),and the time in the target quadrant and the numbers of crossing the platform were increased(P<0.05),the serum levels of CORT,ACTH,and CRH were significantly decreased(P<0.01),the mRNA expression of CRH,CRHR1,CRH-BP in the hypothalamus and CRHR1 and CRH-BP in the pituitary were decreased(P<0.05,P<0.01),while GR protein expr

关 键 词：注意缺陷多动障碍 慢性应激 龙牡桂枝汤 学习记忆能力 下丘脑-垂体-肾上腺轴 海马 

分 类 号：R285.5[医药卫生—中药学]