摘要
目的:探讨开心散对APP/PS1小鼠学习记忆和突触功能的潜在保护机制。方法:将60只APP/PS1小鼠随机分为模型组,多奈哌齐(2 mg·kg^(-1)·d^(-1))组,开心散低、中、高剂量(0.7,1.4,2.8 g·kg^(-1)·d^(-1))组,同月龄同窝野生型小鼠为正常组,每组12只。连续灌胃给药2个月后进行Morris水迷宫实验。采用透射电镜观察海马神经元超微结构。采用比色法检测血清乙酰胆碱(ACh),乙酰胆碱转移酶(ChAT),乙酰胆碱酯酶(AChE)含量和海马活性氧(ROS),丙二醛(MDA),超氧化物歧化酶(SOD),谷胱甘肽过氧化物酶(GSH-Px)水平。采用实时荧光定量聚合酶链式反应(Real time-PCR)检测海马脑源性神经营养因子(BDNF),β-神经生长因子(NGFB),discs大同源物(DLG)2,DLG4,突触素(SYP)mRNA的表达。结果:与正常组比较,模型组小鼠逃避潜伏期明显延长,穿越平台次数,目标象限停留时间显著减少(P<0.01),线粒体数量明显减少,形态各异,排列不规则,部分线粒体明显肿胀,变形,线粒体嵴断裂,胞浆溶解,呈空泡状,细胞碎片较多,血清ACh,ChAT含量显著降低,AChE水平显著升高(P<0.01),海马ROS,MDA明显升高(P<0.05,P<0.01),SOD,GSH-Px显著下降(P<0.01),海马BDNF,NGFB,DLG2,DLG4,SYP mRNA水平明显下降(P<0.05,P<0.01)。与模型组比较,多奈哌齐组和开心散中、高剂量组逃避潜伏期明显缩短,穿越平台次数明显增加,目标象限停留时间明显延长(P<0.05,P<0.01),线粒体损伤改善,形态规则,多呈椭圆形,线粒体肿胀、变形减少,线粒体嵴清晰,血清ACh,ChAT水平明显升高(P<0.05,P<0.01),AChE活性明显下降(P<0.05),海马ROS水平明显降低(P<0.05,P<0.01),MDA水平明显降低(P<0.05),SOD,GSH-Px活性明显增加,海马BDNF,NGFB,DLG2,DLG4,SYP mRNA水平明显升高(P<0.05,P<0.01),开心散低剂量组目标象限停留时间明显延长,海马SYP mRNA水平明显增加(P<0.05),各组间的游泳速度比较,差异无统计学意义。结论:开心散通过提高突触可塑性相关蛋
Objective: To explore the underlying protective mechanism of Kaixinsan on learning,memory,and synaptic function in APP/PS1 mice. Method:Sixty APP/PS1 mice were randomly divided into a model group,a donepezil(2 mg·kg^(-1)·d^(-1))group,and low-(0.7 g·kg^(-1)·d^(-1)),medium-(1.4 g·kg^(-1)·d^(-1)),and high-dose(2.8 g·kg^(-1)·d^(-1))Kaixinsan groups,and the wild-type mice of the same age in the same litter were assigned to the normal group,with 12 mice in each group. After continuous intragastric administration for two months,the Morris water maze experiment was performed. The ultrastructure of hippocampal neurons was observed by transmission electron microscopy. The colorimetric assay was used to detect serum content of acetylcholine(ACh), choline acetyltransferase(ChAT), acetylcholinesterase(AChE), and levels of hippocampal reactive oxygen species(ROS),malondialdehyde(MDA),superoxide dismutase(SOD),and glutathione peroxidase(GSH-Px). Real-time fluorescence-based quantitative polymerase chain reaction(Realtime PCR)was used to detect the mRNA expression of hippocampal brain-derived neurotrophic factor(BDNF),beta-nerve growth factor(NGFB),discs large homolog(DLG)2,DLG4,and synaptophysin(SYP). Result:Compared with the normal group,the model group showed prolonged escape latency,reduced number of crossing platforms,shortened stay in the target quadrant(P<0.01),decreased number of mitochondria with different shapes and irregular arrangement,some swollen and deformed mitochondria with broken mitochondrial cristae,endolysis,and cytoplasm vacuole,and more cell debris. Additionally,the model group also displayed reduced serum levels of ACh and ChAT,increased AChE(P<0.01),elevated hippocampal ROS and MDA(P<0.05,P<0.01),declining SOD and GSH-Px(P<0.01),and diminished hippocampal BDNF,NGFB,DLG2,DLG4,and SYP mRNA levels(P<0.05,P<0.01). Compared with the model group,the donepezil group,and the medium-and high-dose Kaixinsan groups showed shortened escape latency,increased number of crossing platforms,prolonged stay in the
作者
许玉珉
沈晓明
兰瑞
朱世瑞
张杰
路芳梅
王保奇
马云枝
XU Yu-min;SHEN Xiao-ming;LAN Rui;ZHU Shi-rui;ZHANG Jie;LU Fang-mei;WANG Bao-qi;MA Yun-zhi(The First Affiliated Hospital of Henan University of Chinese Medicine,Zhengzhou 450000,China;Henan University of Chinese Medicine,Zhengzhou 450000,China)
出处
《中国实验方剂学杂志》
CAS
CSCD
北大核心
2021年第20期15-22,共8页
Chinese Journal of Experimental Traditional Medical Formulae
基金
国家自然科学基金项目(81904265)
河南省科技攻关项目(192102310166)
河南省中医药科学研究专项(2019JDZX2017)。
关键词
开心散
阿尔茨海默病
突触可塑性相关蛋白
氧化应激
胆碱能神经递质
学习记忆能力
Kaixinsan
Alzheimer’s disease
synaptic plasticity-related proteins
oxidative stress
cholinergic neurotransmitter
learning and memory ability
