瓜子金提取物对D-半乳糖痴呆小鼠的作用及机制研究  

The effect and mechanism of the extract of Polygala japonica Houtt.on dementia-like mice induced by D-galactose

作　　者：刘顶鼎 杨菁 刘冬 凌小力 曾贵荣 周英 LIU Ding-ding;YANG Jing;LIU Dong;LING Xiao-li;ZENG Gui-rong;ZHOU Ying(Guizhou University of Chinese Medicine,Guiyang Guizhou 550025,China;Drug Safety Evaluation Research Center of Hunan Province&Key Laboratory of New Drug Pharmacodynamics and Safety Evaluation of Hunan Province,Changsha Hunan 410331,China)

机构地区：[1]贵州中医药大学,贵州贵阳550025 [2]湖南省药物安全评价研究中心新药药效与安全性评价湖南省重点实验室,湖南长沙410331

出　　处：《时珍国医国药》2020年第8期1796-1798,共3页Lishizhen Medicine and Materia Medica Research

基　　金：国家自然科学基金(81860844);贵州省科学技术基金计划项目(黔科合基础[2016]1016,黔科合基础[2019]1038号);贵州省教育厅青年科技人才成长项目(黔教合KY字[2016]185);贵州省中医药、民族医药科学技术研究专项(QZYY-2016-001);贵州省苗医药重点实验室开放课题(黔苗医药K字[2017]007、黔苗医药K字[2017]031);全国大学生创新创业训练项目(贵中医大创合字(2018)13号);贵阳中医学院一流专业(中药学)大学生创新创业训练计划项目(贵中医一流专业大创合字(2017)158号)。

摘　　要：目的研究瓜子金提取物对D-半乳糖痴呆模型小鼠学习记忆能力的改善作用,初步探讨瓜子金提取物的作用机制。方法雄性ICR小鼠50只,按体重随机分为正常对照组,模型对照组,盐酸多奈哌齐片组(3.0 mg·kg-1),瓜子金提取物低、高(25、100 mg·kg-1)剂量组。除正常对照组外,其余小鼠颈背部皮下注射D-半乳糖(200 mg·kg-1),每天1次,连续6周(42 d),正常对照组皮下注射等容积生理盐水。各组分别灌胃给予相应药液,连续给药6周,末次给药后进行水迷宫和新物体识别行为学实验,实验结束时取小鼠海马组织采用ELISA法检测海马组织脑源生长因子(BDNF)、人β位淀粉样前体蛋白裂解酶1(BACE1)的含量。结果与正常对照组比较,模型对照组定位航行D1-3潜伏期、D2-3总路程明显增加,D2-3速度、经过平台次数明显减少(P<0.05,P<0.01);小鼠辨别指数明显降低(P<0.05);小鼠BDNF含量显著降低,BACE1含量显著升高(P<0.01)。与模型对照组比较,瓜子金提取物低剂量(25 mg·kg-1)能明显减少定位航行D3潜伏期(P<0.05)。瓜子金提取物高剂量(100 mg·kg-1)可明显减少定位航行D2-3潜伏期、D3总路程,明显增加D2速度、经过平台次数(P<0.05);能明显升高小鼠新物体识别辨别指数(P<0.05);能明显升高小鼠海马组织BDNF含量,降低BACE1含量(P<0.05)。结论瓜子金提取物对D-半乳糖痴呆模型小鼠学习记忆能力具有明显的改善作用,其机制可能与BDNF、BACE1等水平变化有关。Objective To study the effect and mechanism of the extract of Polygala japonica Houtt. on dementia-like mice induced by D-galactose.Methods Fifty male ICR mice were randomly divided into the normal control group by weight, the model control group, and the doneperazi group(3.0 mg·kg-1), the low, high(25, 100 mg·kg-1) dose group of the extract of Polygala japonica Houtt.. Except the normal group, the other mice were injected subcutaneously with D-galactose in 200 mg·kg-1, one time a day for 6 weeks(42 days). A normal control group was treated with subcutaneous injection and other volume physiological saline. Groups of gastric gavage corresponding solution, respectively for 6 weeks in a row. After the last administration, the water maze and new object recognition behavior experiments were performed. At the end of the experiment, the content of brain-derived growth factor(BDNF) and human β-amyloid precursor protein lyase 1(BACE1) in mouse hippocampus was detected by ELISA.Results Compared with normal group, the incubation period of D1-3 and total distance of D2-3 in model group were increased significantly, the speed of D2-3 and space exploration were decreased significantly(P<0.05, P<0.01). The recognition of new objects was decreased significantly(P<0.05). The content of BDNF in the hippocampal tissue of mice was decreased obviously, and BACE1 was increased obviously(P<0.01). Comparison of model group, the low dose(25 mg·kg-1) of the extract of Polygala japonica Houtt. can significantly reduce the incubation period of D3(P<0.05). The high dose(100 mg·kg-1) of the extract of Polygala japonica Houtt. can significantly reduce the incubation period of D2-3 and total distance of D3, and can significantly increase the speed of D2 and space exploration and the recognition of new objects(P<0.05). It can significantly increase the content of BDNF in the hippocampal tissue of mice, and reduce the content of BACE1(P<0.05). Conclusion The extract of Polygala japonica Houtt. can improve the learning and memory of D-galact

关 键 词：瓜子金提取物 D-半乳糖 痴呆 脑源生长因子 人β位淀粉样前体蛋白裂解酶1 

分 类 号：R285.5[医药卫生—中药学]