摘要
目的:考察给予东莨菪碱造模后,补阴益智汤配方颗粒对小鼠学习记忆损伤的保护作用,并通过神经递质和突触可塑性相关蛋白考察其可能的机制。方法:雄性昆明种小鼠50只,通过腹腔注射东莨菪碱(3.0 mg·kg^(-1))建立小鼠学习记忆损伤模型。随机分为正常组、模型组和补阴益智汤高、中、低(18,6,2 g·kg^(-1)),造模后,连续给药2周,通过小鼠跳台实验,Morris水迷宫实验和新物体辨别实验,考察小鼠学习记忆的能力。采用高效液相色谱法测定小鼠前额叶皮层和海马内氨基酸类神经递质的水平,通过蛋白质免疫印迹法(Western blot)检测小鼠海马区内突触核蛋白(Syn),突触后密度蛋白-95(PSD-95)和脑源性神经营养因子(BDNF)蛋白的表达。结果:与正常组比较,模型组小鼠跳台实验、水迷宫实验潜伏期显著缩短(P<0.01),触电次数显著增加(P<0.01),对新物体的探索时间显著缩短(P<0.01),海马及前额叶皮层内γ-氨基丁酸(GABA)含量增多,而谷氨酸(Glu)含量均显著降低(P<0.01),海马内Syn,PSD-95和BDNF蛋白表达量均明显增多(P<0.05,P<0.01);与模型组比较,中、高剂量给药组潜伏期明显延长(P<0.05,P<0.01),其中高剂量组触电次数明显减少(P<0.05);对新物体的探索时间显著延长(P<0.01),GABA含量明显降低(P<0.05,P<0.01),Glu含量以及Syn,PSD-95和BDNF蛋白表达量明显升高(P<0.05,P<0.01)。结论:补阴益智汤配方颗粒可以改善东莨菪碱所致的小鼠学习记忆损伤,其机制可能与改变海马及前额叶皮层内Glu/GABA以及调节小鼠海马脑区内Syn和PSD-95蛋白的表达有关。
Objective： To study the effect of Buyin Yizhi decoction on learning and memory disorder induced by scopolamine, and investigate its possible mechanism through neurotransmitter and synaptic plasticity related proteins. Method： The learning and memory disorder models were established by intraperitoneal injection of scopolamine （3.0 mg·kg^-1 ） in 50 male Kunming mice. Then these mice were randomly divided into normal blank group, model group and Buyin Yizhi decoction high dose group （18 g·kg^-1） , middle dose group （6 g·kg^-1） , and low dose group （2 g·kg^-1）. The treatment lasted for 2 weeks after modeling. Step-down test, Morris water maze test and novel object test were used to explore the the ability of learning and memory in mice. Meanwhile, the amino acid neurotransmitter levels in prefrontal cortex and hippocampus of the mice were determined by high performance liquid chromatography （ HPLC ）. The expression levels of Synembry （ Syn）, PSD-95 and brain derived neurotrophic factor （BDNF） in hippocampus were determined by Western blot. Result： As compared with the normal blank group, the latency in step-down test and Morris water maze test was shortened significantly in model group （ P 〈0. 01 ） ; the electric shocks number was increased （ P 〈 0.01 ） ; and the exploration time of new object was shortened （P 〈0. 01） ; at the same time, the contents of gamma-aminobutyric acid （GABA） was increased while the contents of glutamic acid （Glu） were reduced （ P 〈 0.01 ） in hippocampus and prefrontal cortex ; and the expression levels of Syn, PSD-95 and BDNF protein were reduced in hippocampus. As compared to the model group, the latency was significantly prolonged in middle and high dose groups （P 〈0.05, P 〈0.01 ） ; the number of electric shocks in the high dose group was decreased significantly （P 〈 0. 05 ）, and the exploration time of new objects was significantly prolonged （ P 〈 0. 05 ） ; GABA content was significantly reduced （
出处
《中国实验方剂学杂志》
CAS
CSCD
北大核心
2017年第12期138-144,共7页
Chinese Journal of Experimental Traditional Medical Formulae
基金
遵义医学院2016博士启动课题(F-814)
遵义市临床药学重点实验室经费项目[省市科合(2015)53号]
关键词
补阴益智汤
东莨菪碱
学习记忆损伤
行为学
神经递质
突触可塑性
Buyin Yizhi decoction
scopolamine
learning and memory
behavior
neurotransmitter
synaptic plasticity
