基于中医方证代谢组学分析四物汤对自然衰老小鼠的干预作用  

Analysis of Effect of Siwutang on Natural Aging Mice Based on Chinmedomics

作　　者：西旺 闫起 王燕[1] 李奇玮[1] 梁华[1] XI Wang;YAN Qi;WANG Yan;LI Qi-wei;LIANG Hua(Heilongjiang University of Chinese Medicine, Harbin 150040,China)

机构地区：[1]黑龙江中医药大学,哈尔滨150040

出　　处：《中国实验方剂学杂志》2019年第12期9-14,共6页Chinese Journal of Experimental Traditional Medical Formulae

基　　金：国家自然科学基金项目(81473563)

摘　　要：目的:通过代谢组学的研究方法观察四物汤对自然衰老小鼠体内代谢物、代谢通路的影响,分析四物汤干预自然衰老小鼠的相关靶点和作用机制。方法:选取20月龄自然哀老模型小鼠(相当于人类60～65岁)作为实验对象,同时设立3月龄小鼠作为青年组。运用UPLC-Q-TOF-MS技术对小鼠血浆进行分析,流动相含0. 1%甲酸的乙腈溶液(A)-0. 1%甲酸水溶液(B)梯度洗脱(0～15 min,2%～100%A),选择电喷雾离子源的正离子模式;采用主成分分析(PCA)和正交偏最小二乘法-判别分析(OPLS-DA)研究代谢标志物,并归纳其代谢途径。结果:四物汤对16种衰老相关代谢物的表达水平有明显回调作用,其中9种代谢标志物存在极显著统计学意义(P <0. 01);主要影响了谷胱甘肽代谢、嘧啶代谢、精氨酸和脯氨酸代谢、硒氨基酸代谢等代谢途径。结论:四物汤可影响20月龄自然衰老小鼠血浆中的代谢物,通过谷胱甘肽代谢、嘧啶代谢、精氨酸和脯氨酸代谢等途径改善小鼠衰老过程中的代谢紊乱,可为该复方后续的干预衰老物质基础研究提供生物学信息。Objective: Through metabonomics research methods,the effect of Siwutang on metabolites and metabolic pathways in natural aging mice were observed. The related targets and mechanism of Siwutang intervention in natural aging mice were analyzed. Method: Taking 20-month-old natural aging model mice( equivalent to 60-65 years old of human beings) as the experimental subjects,at the same time,mice aged 3 months were established as the youth group. UPLC-Q-TOF-MS technique was employed to analyze the mouse plasma with mobile phase of acetonitrile( containing 0. 1% formic acid)-0. 1% formic acid solution for gradient elution and positive ion mode of electrospray ionization,and the metabolic markers were analyzed by principal component analysis( PCA) and orthogonal partial least squares-discriminant analysis( OPLS-DA), and their metabolic pathways were summarized. Result: Siwutang had obvious reversal effect on the expression levels of 16 aging-related metabolites,among which 9 metabolic markers were statistically significant( P < 0. 01),mainly affecting glutathione metabolism,pyrimidine metabolism,arginine and proline metabolism,selenium amino acid metabolism and other metabolic pathways. Conclusion: Siwutang can affect the metabolites in the plasma of 20-month-old natural aging mice,and the metabolic disorder during the aging process of mice can be improved by glutathione metabolism,pyrimidine metabolism,selenium amino acid metabolism and other pathways,and this paper can provide biological information for the study of material basis of this compound for aging.

关 键 词：四物汤 衰老 中医方证代谢组学 血虚证 谷胱甘肽 自然衰老模型 代谢标记物 

分 类 号：R22[医药卫生—中医基础理论] R24[医药卫生—中医学]