目的 运用代谢组学方法分析淫羊藿95％乙醇洗脱部位(E95EE)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,探究其标志物表达的差异是否会随体液循环分布影响机体的不同系统,从而产生潜在的保护或毒性作用.方法 SD大鼠随机分为正常对照组和E95EE给药组,各10只,E95EE组ig给予E95EE 17.1 g·L-1,1/d,连续20 d.正常对照组以等量生理盐水代替,于末次给药后用代谢笼收集大鼠12 h尿液,处理后进行UPLC-TOF/MS分析.结果 鉴定出9个差异性的内源性代谢产物,即3-sn-磷脂酸、l-1磷脂酰乙醇胺、草酰乙酸、甲酰-N-乙酰-5-甲氧基犬尿素烯胺、N-乙酰-5-羟色胺、5,10-甲酰四氢叶酸、N-亚氨代甲基l-l-谷氨酸盐、1-酰基甘油酮3-磷酸盐和亚硫酸;6条主要代谢通路,即柠檬酸的乙酰辅酶A生物合成、组氨酸代谢、甘油三酯代谢、色氨酸代谢、维生素A代谢、糖酵解与糖异生;推测E95EE可能通过降低3-sn-磷脂酸和草酰乙酸水平,上调N-亚氨代甲基l-l-谷氨酸盐的表达,从而对神经、心血管系统发挥保护作用;可能通过降低5,10-甲酰四氢叶酸和l-1磷脂酰乙醇胺水平,增加肿瘤发生的风险.结论 E95EE对正常大鼠神经系统、心脑血管系统、免疫系统及肿瘤相关疾病存在药效与毒性并存的干预作用,其作用机制与甘油三酯代谢、维生素A代谢和色氨酸和组氨酸代谢等通路有关.%OBJECTIVE To observe the effect of Epimedium 95％ethanol elution section (E95EE) on endogenous metabolism in the urine of normal rats using methods of metabonomics, and to study whether differential expressions of biomarkers can influence different systems of the body along with various body-fluids-cycle distribution. METHODS SD rats were randomly divided into blank control group and E95EE group(10 rats per group). The rats of E95EE group were ig administered with E95EE 17.1 g · L-1, once daily, for 20 d, while those of normal control group were ig given an equal volume of saline. On the day of the final E95EE administration, the urine of 12 h was collected for analysis by UPLC-TOF/MS. RESULTS This study identified nine differential endogenous metabolites (3-sn-phos-phatidate, 5, 10-methenyltetrahydrofolate, l-1-phosphatidylethanolamine, 1-acyl-glycerone 3-phosphate, N-formimidoyl-l-glutamate, keto-oxaloacetate, sulfurous acid, formyl-N-acetyl-5-methoxykynurenamin and N-acetyl-5-hydroxytryptamine) and six primary metabolic pathways [glycerophospholipid metabolism, vitamin A (retinol) metabolism, histidine degradation, tryptophan metabolism, acetyl-CoA biosynthesis from citrate, glycolysis and gluconeogenesis]. The possible role of protection of E95EE discovered in the nervous and cardiovascular systems was displayed by the decreased level of 3-sn-phosphatidate and an increased level of N-formimidoyl-l-glutamate. However, the possible toxicity of E95EE on neoplastic prevention was achieved by reducing the level of l-1-phosphatidylethanolamine and 5,10-methenyl tetra-hydrofolate. CONCLUSION E95EE can produce both protection and toxicity on nervous, cardiovascular and immune systems, as well as on tumor-associated diseases. The mechanisms may be related to metabolic pathways of triglycerides, vitamin A, tryptophane and histidines.
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