运用代谢组学方法初筛刺五加多糖的药理作用及机制  

Application of Metabonomics Method to Identify Possible Effect of Acanthopanax senticosus Polysaccharide on AD

作　　者：卢芳[1] 杨晓丹[1] 井月娥[1] 张娜[1] 刘树民[2] 

机构地区：[1]黑龙江中医药大学中医药研究院,哈尔滨150040 [2]黑龙江中医药大学药物安全性评价中心,哈尔滨150040

出　　处：《中国实验方剂学杂志》2015年第22期150-153,共4页Chinese Journal of Experimental Traditional Medical Formulae

基　　金：国家自然科学基金青年-面上连续资助项目(81270056);高等学校博士学科点专项科研基金(博导类)(20132327110009);黑龙江省普通高等学校新世纪优秀人才培养计划项目(1254-NCET-020);黑龙江中医药大学科研基金项目(杰出人才培育基金)(2013jc01);黑龙江中医药大学优秀创新人才支持计划项目

摘　　要：目的:运用代谢组学方法考察刺五加多糖对正常生理状态大鼠内源性物质代谢的影响,寻找潜在的生物标志物并分析其代谢途径,探讨其药理作用及作用机制。方法:SD大鼠随机分为空白组和刺五加多糖给药组,各10只,分别给予生理盐水(灌胃容积为10 m L·kg-1)和刺五加多糖(100 mg·kg-1),连续灌胃20 d,于第21日收集尿样,经处理供UPLC-Q-TOF/MS分析,本实验采用Micromass Markerlynx软件进行色谱峰识别以及峰匹配,并采用主成分分析法(PCA)和正交偏最小二乘判别分析法(O-PLS-DA)对获得的多维复杂数据进行降维处理。通过对空白组和刺五加多糖给药组大鼠尿样代谢指纹数据进行分析,根据质荷比匹配生物标志物并查找其代谢途径。结果:鉴定出6-二甲基氨基嘌呤,L-乙酰肉碱等20个潜在生物标志物,并且其药理活性与神经保护、抗细胞凋亡等有关。结论:刺五加多糖对阿尔茨海默病和心血管疾病(CVD)等疾病有一定的药理作用,其作用机制可能与细胞凋亡和兴奋毒性等假说相关。Objective： To observe the effect of Acanthopanax senticosus polysaccharides（ ASPS） on endogenous metabolites in normal rats using metabolomics method,find potential biomarkers,analyze the metabolic pathways,and explore its pharmacological effects and mechanisms of action. Method： Twenty SD rats were randomly divided into two groups,namely 10 in the blank group with normal saline treatment（ 10 m L·kg^- 1） and10 in ASPS group with ASPS treatment（ 100 mg·kg^- 1） for 20 days respectively. Urine samples were collected on day 21 for UPLC-Q-TOF / MS analysis. Micromass Markerlynx software was adopted for chromatographic peak identifying and peaks matching,and the principal component analysis（ PCA） and orthogonal partial least squares discriminant analysis（ O-PLS-DA） were used for dimension reduction process for the complex multi-dimensional data. Based on the metabolic fingerprinting data analysis of urine samples in blank group and ASPS group,biomarkers were matched according to mass to charge ratio,and their metabolic pathway was identified. Result：Twenty potential biomarkers such as 6-dimethylaminopurine and L-acetylcarnitine were identified, and their pharmacological activity was found to be related to neuroprotection and resisting cell apoptosis. Conclusion： ASPS has a certain pharmacological effects on Alzheimer＇s disease,cardiovascular disease and other diseases,and its mechanism may be related to cell apoptosis and excitotoxic hypothesis.

关 键 词：刺五加多糖 代谢组学 生物标志物 阿尔茨海默病 心血管疾病 

分 类 号：R284.1[医药卫生—中药学]