从基因表达谱和代谢组学角度探讨淫羊藿总黄酮延缓衰老的效应及机制  

Effect and Mechanism of Epimedium Flavanoids for Aging Retardation from Viewpoint of Transcriptomics and Metabonomics

作　　者：黄建华[1] 沈自尹[1] 吴斌[1] 刘小雨[2] 林伟[3] 

机构地区：[1]复旦大学附属华山医院中西医结合研究所,上海200040 [2]同济大学附属第十人民医院中医科 [3]复旦大学数学系

出　　处：《中国中西医结合杂志》2008年第1期47-50,共4页Chinese Journal of Integrated Traditional and Western Medicine

基　　金：国家自然科学基金资助项目(No．904090010);上海市科委重点基础研究计划(No．04JC14090);上海市卫生局中医药科研基金课题(No．2004J014A)

摘　　要：目的用系统观点从不同角度揭示淫羊藿总黄酮(EF)延缓衰老的效应及机制方法50只SD大鼠分为4、10、18、24月龄组和EF组共5组,EF组大鼠自21月龄开始灌胃EF至24月龄。摘取大鼠下丘脑、垂体、肾上腺、淋巴细胞等组织,进行基因芯片检测;取血清,利用高效液相和质谱进行代谢组检测;利用专用芯片检测淋巴细胞NF-κB信号通路相关分子基因表达。利用上述数据,建立神经网络模型,评价衰老程度和药物干预的效果。结果199个基因表达具年龄依赖特征,EF能逆转大部分基因表达,神经网络模型输出显示EF使24月龄大鼠基因表达年轻化至8～13月龄;代谢组检测共获得1 885个代谢物谱峰,已鉴定17个代谢物随增龄变化显著,EF干预使代谢物水平年轻化至18月龄;NF-κB信号通路基因表达整体水平随增龄而降低,EF使之上升,神经网络模型显示向10.5月龄靠近。结论不同层面的衰老表型首先表现为均具有年龄依赖关系;EF能逆转不同层面的增龄性变化,具有同步的表现。Objective To investigate the effect and its mechanism of epimedium flavanoids （EF） in retarding aging with different systematic viewpoints. Methods Hypothalamus, pituitary, adrenal and lymphocytes taken from 4-, 10-, 18-, 24-month old rats and from EF treated 24-month old rats were used to measure whole genome mRNA expression by gene array. Serum samples were used for metabonomic assay with high performance liquid chromatography. Using specific gene chip for NF-κB signaling pathway to detect the gene expression of the molecule related to that pathway in lymphocytes. Then, a neural network （NN） model was established upon the data obtained to quantitatively evaluate the degree of aging and the efficacy of drug intervention. Results Gene expression of 199 genes showedan age-dependent pattern, most of which were reversed by EF, and the output of NN model showed that EF made the transcriptomics of 24-month old rats to 8-13 months. Seventeen metabolites among the 1 885 peaks detected were identified to have significant age-depending changes, and EF intervention reset the level of metabolites to a younger （18-month） level. The integral level of gene expression for NF-κB signaling pathway decreased significantly along with the increasing of age, and was significantly elevated by EF, NN model showed it approached to 10. 5-month old. Conclusion Phenotype of aging at different levels demonstrates a common age-dependent trend; EF can reverse this age-dependent change at different levels in a synchronous manner.

关 键 词：基因表达谱 代谢组 衰老 淫羊藿总黄酮 

分 类 号：R285[医药卫生—中药学]