五味子治疗大鼠糖尿病肾病作用机制的血清代谢组学研究  

Serumal Metabonomic Study on Mechanism of Schisandra Chinensis in Rat Diabetic Nephropathy

作　　者：皮子凤[1] 门丽慧[2] 张静[2] 周园[2] 宋凤瑞[1] 刘志强[1] 

机构地区：[1]中国科学院长春应用化学研究所国家质谱中心(长春)吉林省中药化学与质谱重点实验室,长春130022 [2]吉林大学药学院,长春130021

出　　处：《分析化学》2015年第2期169-175,共7页Chinese Journal of Analytical Chemistry

基　　金：国家自然科学基金(No.81373952)资助~~

摘　　要：采用基于超高效液相色谱与串联四级杆飞行时间质谱仪(Ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry,UPLC/Q-TOF-MS)联用技术的代谢组学方法,通过分析大鼠血清内源性代谢物的变化,研究五味子治疗糖尿病肾病的作用机制。利用高脂高糖饲料喂养并腹腔注射链脲佐菌素(STZ)建立糖尿病大鼠模型。给药12周后,采用试剂盒方法测定尿蛋白、尿肌酐的含量,结果表明五味子水提取物可以显著降低模型动物的尿蛋白含量(p<0.05),对糖尿病大鼠肾病并发症具有一定的改善作用。采用UPLC/Q-TOF-MS方法分析了五味子对糖尿病肾病大鼠的血清代谢轮廓,分析了健康组、模型组和五味子给药组的大鼠血清,采用偏最小二乘法-判别分析(Partial least squares discriminant analysis,PLS-DA)进行数据分析。PLS-DA得分图显示健康组、模型组和五味子组的代谢轮廓有显著差别,根据正交偏最小二乘法-判别分析(Orthogonal partial least squares discriminant analysis,OPLS-DA)载荷图筛选,将对各组分离贡献大的化合物的串联质谱分析数据,经Human Metabolome Database(HMDB)等数据库检索,进行质谱信息匹配,鉴定出黄尿酸、油酰胺、棕榈酰胺、尿酸、5-羟基己酸、硫酸对甲酚、对甲酚葡萄糖苷酸7种内源性代谢物为生物标记物。研究结果表明五味子通过影响色氨酸代谢、嘌呤代谢、肠内菌代谢、脂肪酸代谢等通路对糖尿病肾病发挥治疗作用,其中嘌呤代谢、肠内菌代谢通路可能是五味子发挥治疗作用的重要途径。A serumal metabonomics method based on UPLC/Q-TOF-MS was established to investigate the mechanism of Schisandra chinensis to treating diabetic nephropathy. The diabetic model was established by feeding with high-fat and high-sucrose chow and streptozotocin intraperitoneal injection. After intragastric administration for 12 weeks, the content of protein and creatinine in rat urine was detected. The results showed that Schisandra chinensis could reduce the content of protein in urine of diabetic rat （ p〈0 . 05 ） and ameliorate the condition of diabetic nephropathy. The serum metabolic profiling was analysed by using UPLC/Q-TOF-MS and partial least squares-discriminated analysis （ PLS-DA） was used for data analysis. The score of PLS-DA showed that there was significant difference among the metabolic profile of control group, model group and Schisandra chinensis group （ WWZ ） . Potential biomarkers of Schisandra chinensis ameliorating diabetic nephropathy were selected by orthogonal partial least squares （ OPLS）-DA model. According to the results of OPLS-DA, the MS/MS data of each compound which provided greater contribution to separation of each group were searched from the HMDB databases. Seven endogenous metabolites were identified as potential biomarkers such as xanthurenic acid, palmitic amide, oleamide, uric acid, 5-hydroxyhexanoic acid, p-cresol sulfate, and p-cresol glucuronide. The results revealed that Schisandra chinensis mainly affected the pathways of tryptophan metabolism, gut microbiota metabolism, purine metabolism and fatty acid metabolism to treating type 2 diabetes mellitus. The gut microbiota metabolism and purine metabolism was an important pathway on diabetic nephropathy.

关 键 词：五味子 糖尿病肾病 血清 代谢组学 

分 类 号：R259[医药卫生—中西医结合] R277.5[医药卫生—中医内科学]