基于BDNF/TrkB通路探讨清心开窍方对APP/PS1双转基因小鼠学习记忆能力的影响

doi:10.13193/j.issn.1673-7717.2024.03.032

科研成果详情

题名	基于BDNF/TrkB通路探讨清心开窍方对APP/PS1双转基因小鼠学习记忆能力的影响
其他题名	Effects of Qingxin Kaiqiao Formula(清心开窍方)on Learning and Memory Ability of APP/PS1 Double Transgenic Mice Based on BDNF/TrkB Pathway
作者	王柳莺1,2; 赖晓晓 2; 刘硕1,2; 徐露婷 2; 沈燕 2; 胡海燕1,2
发表日期	2023-08-29
发表期刊	中华中医药学刊影响因子和分区
语种	中文
原始文献类型	学术期刊
关键词	阿尔兹海默症清心开窍方 BDNF/TrkB通路淀粉样前体蛋白/早老素-1双转基因小鼠
其他关键词	Alzheimer's disease ; Qingxin Kaiqiao Formula(清心开窍方) ; BDNF/TrkB pathway ; APP/PS1 mice
摘要	目的基于脑源性神经营养因子（brain-derived neurotrophic factor，BDNF）/原肌球蛋白相关激酶B（Tropomyosin-related kinase B，TrkB）通路探讨清心开窍方对淀粉样前体蛋白/早老素-1（APP/PS1）双转基因小鼠认知功能及神经元保护作用的影响。方法将30只APP/PS1小鼠按照随机数字表法分为模型组、安理申组(1.67 mg·kg－1·d－1)、清心开窍方低剂量组(4.75mg·kg－1·d－1)、清心开窍方中剂量组(9.5mg·kg－1·d－1)和清心开窍方高剂量组(19mg·kg－1·d－1) 。选取6只雄性C57/B6小鼠记为对照组，连续90天于每日上午9点进行灌胃。完成灌胃后，通过Morris水迷宫测试小鼠的空间学习记忆能力；通过HE染色观察小鼠海马CA1区细胞形态变化；通过尼氏染色观察小鼠海马CA1区病理形态变化；通过实时荧光定量聚合酶链式反应（Real-time qPCR）检测β位淀粉样前体蛋白裂解酶1（BACE1）、TrkB、BDNF mRNA在小鼠海马中的表达；通过蛋白免疫印迹法（Western blotting，WB）检测蛋白P-TrkB、TrkB、BACE1、BDNF蛋白的表达水平。结果与对照组相比，模型组小鼠逃避潜伏期明显增多（P<0.01），而穿越平台次数以及在原平台所在象限滞留的时间明显增多（P<0.01），其小鼠海马神经元出现严重损伤，排列松散，尼氏体数量减少，染色变浅，BACE1表达增加（P<0.01），P-TrkB、TrkB、BDNF表达降低（P<0.01）；与模型组相比，清心开窍方治疗组逃避潜伏期缩短，穿越平台次数以及目标象限停留时间明显增多（P<0.05或P<0.01），小鼠海马锥体细胞排列较紧密，形态完整，尼氏体数目增加，着色加深，BACE1表达降低（P<0.05或P<0.01），P-TrkB、TrkB、BDNF表达增加（P<0.05或P<0.01）。结论清心开窍方可能通过BDNF/TrkB通路改善 APP / PS1小鼠学习记忆能力，对神经细胞起保护作用。
其他摘要	Objective To investigate the effects of Qingxin Kaiqiao Formula(清心开窍方)on cognitive function and neuronal protection in amyloid precursor protein(APP)/presenilin-1(PS1)double transgenic mice based on brain-derived neurotrophic factor(BDNF)/tropomyosin-related kinase B(TrkB)pathway.Methods Thirty APP/PS1 mice were divided into the model group,Aricept group(1.67 mg·kg-1·d-1),Qingxin Kaiqiao Formula low dose group(4.75 mg·kg-1·d-1),Qingxin Kaiqiao Formula medium dose group(9.5 mg·kg-1·d-1)and Qingxin Kaiqiao Formula high dose group(19 mg·kg-1·d-1)according to the random number table method.Six male C57/B6 mice were selected as the control group and given the drugs by gavage at 9:00 am daily for 90 days.After gavage,the spatial learning memory of the mice was tested by Morris water maze.The cell morphological changes in the CA1 region of the hippocampus were observed by HE staining.The pathological morphological changes in the CA1 region of the hippocampus were observed by Nissl staining.The expressions of TrkB,β amyloid precursor protein lyase 1(BACE1)and BDNF mRNA in the hippocampus of the mice wre detected by real-time fluorescence quantitative polymerase chain reaction(Real-time qPCR).The expression levels of protein P-TrkB,TrkB,BACE1 and BDNF proteins were detected by protein immunoblotting(Western blotting,WB).Results Compared with those in the control group,the mice in the model group showed a significantly higher escape latency(P＜0.01),a significantly higher number of platform crossings and a significantly longer retention time in the quadrant of the original platform(P＜0.01),severe damage to hippocampal neurons,loo-ser arrangement,reduced number of nisomes,lighter staining,increased expression of BACE1(P＜0.01)and decreased expres-sions of P-TrkB,TrkB and BDNF expression(P＜0.01).Compared with the model group,the Qingxin Kaiqiao Formula treat-ment groups had a shorter escape latency,a significantly higher number of crossing platforms and a longer dwell time in the target quadrant(P＜0.05 or P＜0.01),a tighter arrangement of hippocampal pyramidal cells,an intact morphology,an increase in the number of nisomes,a deeper coloration,a lower expression of BACE1(P＜0.05 or P＜0.01)and increased expressions of P-TrkB,TrkB and BDNF(P＜0.05 or P＜0.01).Conclusion Qingxin Kaiqiao Formula may improve the learning memory ability of APP/PS1 mice through the BDNF/TrkB pathway and plays a protective role on neural cells.
资助项目	国家自然科学基金项目：MAPK/mTOR/IR/IGF-1R信号通路与清心开窍方对双转基因小鼠脑内SP形成作用及机制（81573896）;浙江省自然科学基金项目：基于IR/IGF-1R信号通路研究清心开窍方干预APP/PS1转基因小鼠SP形成的机制（LY15H270016）
ISSN	1673-7717
卷号	42 期号:03 页码:1-19
DOI	10.13193/j.issn.1673-7717.2024.03.032
页数	19
收录类别	北大核心 ; 万方 ; 维普 ; CNKI
URL	查看原文
引用统计
文献类型	期刊论文
条目标识符	https://kms.wmu.edu.cn/handle/3ETUA0LF/182549
专题	第二临床医学院、附属第二医院、育英儿童医院附属第二医院附属第二医院_中医科
通讯作者	胡海燕
作者单位	1.温州医科大学附属第二医院中医科; 2.温州医科大学第二临床医学院
第一作者单位	附属第二医院; 第二临床医学院，附属第二医院、育英儿童医院; 中医科
第一作者的第一单位	附属第二医院
推荐引用方式 GB/T 7714	王柳莺,赖晓晓,刘硕,等. 基于BDNF/TrkB通路探讨清心开窍方对APP/PS1双转基因小鼠学习记忆能力的影响[J]. 中华中医药学刊,2023,42(03):1-19.
APA	王柳莺, 赖晓晓, 刘硕, 徐露婷, 沈燕, & 胡海燕. (2023). 基于BDNF/TrkB通路探讨清心开窍方对APP/PS1双转基因小鼠学习记忆能力的影响. 中华中医药学刊, 42(03), 1-19.
MLA	王柳莺,et al."基于BDNF/TrkB通路探讨清心开窍方对APP/PS1双转基因小鼠学习记忆能力的影响".中华中医药学刊 42.03(2023):1-19.