运用代谢组学方法探讨淫羊藿水段组分对代谢轮廓靶点的干预作用  

Investigation of Intervention of Epimedii Folium Water Extract on Metabolic Profiling Targets by Metabonomics

作　　者：郭艳霞[1] 杨晓旭[1] 王宇[1] 刘树民[1] 

机构地区：[1]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》2017年第14期86-92,共7页Chinese Journal of Experimental Traditional Medical Formulae

基　　金：国家重点基础研究发展计划(973计划)项目(2013CB531804);黑龙江中医药大学科研基金项目(201419)

摘　　要：目的:运用代谢组学方法分析淫羊藿水段组分对正常大鼠尿液中内源性物质代谢的影响,通过寻找相关代谢途径及潜在作用靶点来探究其标志物表达的差异是否会随着体液代谢的循环分布影响着机体的不同系统功能,从而产生潜在的干预作用。方法:SD大鼠分为空白组和淫羊藿水段组分给药组,每组10只,给药组每天按87.3 mg·kg^(-1)给予淫羊藿水段组分1次,空白组给予等量生理盐水,连续灌胃20 d,于最后1次给药后用代谢笼收集大鼠12 h尿液,经处理供UPLC-Q-TOF/MS分析,正离子扫描模式下电喷雾离子源(ESI),毛细管电压1.3 k V,样本锥孔电压60 V;负离子扫描模式下ESI,毛细管电压1.5 k V,样本锥孔电压70 V。结果:鉴定出10个潜在生物标志物,6条主要代谢通路,发现淫羊藿水段组分可通过N,N'-双(3-氨基丙基)-1,4-丁二胺,N-(3-氨基丙基)-1,4-丁二胺的高表达起到对心脑血管疾病的保护作用,低表达的N-(ω)羟基-L-精氨酸和β-酪氨酸分别表现出不利于肿瘤和神经性疾病的预防。结论:淫羊藿水段组分对正常大鼠心脑血管疾病有显著的保护作用;对神经系统及肿瘤相关疾病存在着药效与毒性共存的特点。其作用机制与氧化胺代谢、酪氨酸代谢、鞘脂类代谢、精氨酸和脯氨酸代谢等通路有关。Objective： Metabonomics was utilized to explore the effect of Epimedii Folium water extract （EWE） on the endogenous metabolism in the urine of normal rats, and to search for related metabolic pathways and potential targets to explore whether the differences of the biomarker＇s expression will affect the different functions of human systems along with the circular distribution of body fliuds, and then produce the potential intervention. Method： Rats have been randomly divided into the blank and EWE groups （10 rats per group） and been garaged the same amount of physiological saline and EWE （87.3 mg＇kg 1） for 20 days, respectively. The urine was gathered on the 21th days for analysis by UPLC-Q-TOF/MS. Result： Ten potential biomarkers and six major metabolic pathways were identified, and it found that EWE could protect the cardiovascular and cerebrovaseular systems via elevating the expression of N, N＇-bis （3-aminopropyl） -1, 4-butanediamine and N- mmo-ro yl） -1 4-butane-diamine. However, the EWE manifested adverse prevention from tumorous and neurological diseases through reduced expression of N- （ω） -hydroxy-L-arginine and β-tyrosine. Conclusion： EWE has a significantly protective effect on the cardiovascular and cerebrovascular diseases of normal rats; however, the potency and toxicity may coexist for the tumorous and neurological diseases. Its mechanisms are related to the metabolic pathway of amine oxide, tyrosine, sphingolipid and so on.

关 键 词：淫羊藿 水段组分 代谢组学 生物标志物 靶点干预 鞘磷脂 

分 类 号：R969.1[医药卫生—药理学] R285.5[医药卫生—药学]