慢性高尿酸血症肾病模型大鼠尿液和肾脏的代谢组学研究  

Metabolomic analysis of urine and renal tissues in rats with chronic hyperuricaemic nephropathy

作　　者：邵晓妮 吴美薇 黑亚南 孙英凯 SHAO Xiao-ni;WU Mei-wei;HEI Ya-nan;SUN Ying-kai(College of Pharmacy,Southwest Minzu University,Chengdu 610041,China)

机构地区：[1]西南民族大学药学院,四川成都610041

出　　处：《中国药理学通报》2020年第11期1607-1614,共8页Chinese Pharmacological Bulletin

基　　金：国家自然科学基金资助项目(No 81801086);西南民族大学中央高校基本科研业务费专项资金资助项目(No 2019HQZZ19)。

摘　　要：目的建立慢性高尿酸血症肾病大鼠模型,探索其特征生物标志物并分析相关代谢通路,为其机制研究提供参考。方法采用含2%尿酸和2%氧嗪酸钾的高尿酸复合饲料饲喂大鼠12周,并利用核磁共振氢谱(1H-NMR)代谢组学技术分析大鼠尿液和肾脏中的差异代谢物。结果组织病理学及血清尿酸、尿素氮、肌酐和葡萄糖检测结果均显示慢性高尿酸血症可诱发大鼠肾功能损伤;通过1H-NMR技术在大鼠尿液和肾脏中筛选出51和48种差异代谢物,其中共有差异代谢物为26种。葡萄糖、牛磺酸、精氨酸、苹果酸、天冬氨酸、谷氨酰胺、谷氨酸和甲基腺嘌呤均有明显变化,可能作为慢性高尿酸血症肾病的特征生物标志物,与肾功能损伤的发生和发展密切相关。结论慢性高尿酸血症肾病大鼠的糖酵解、三羧酸循环、精氨酸代谢及氧化应激等发生特异性变化,且筛选的差异代谢物可为其机制研究奠定理论基础。Aim To establish the rat model of chronic hyperuricaemic nephropathy,explore its characteristic biomarkers and analyze the related metabolic pathways,in order to provide reference for identifying the molecular mechanism.Methods The rats were treated with 2% w/w uric acid and 2% w/w oxonic acid diet for 12 weeks.The changes of metabolites in urine and renal tissues of rats were analyzed by 1H nuclear magnetic resonance(1H-NMR)based metabolomics assay.Results Renal histopathology and serum uric acid,blood urea nitrogen,serum creatinineand serum glucose levels showed that hyperuricaemia induced chronic renal injury in rats.All together 51 and 48 differential metabolites were identified respectivelyin urine and renal tissues using 1H-NMR based metabolomics assay,and 26 same differential metabolites were identifiedamong them.The levels of glucose,taurine,arginine,malate,aspartate,glutamine,glutamate and methyladenine had significant changes.These differential metabolites might be characteristic biomarkers for chronic hyperuricaemic nephropathy and correlated with the progression of renal injury.Conclusions Glycolysis,tricarboxylic acid cycle,arginine metabolism and oxidative stress are disturbed in rats with chronic hyperuricaemic nephropathy.The differential metabolites provide the theoretical foundation for further exploration of the underlying mechanisms of chronic hyperuricaemic nephropathy.

关 键 词：慢性高尿酸血症肾病 尿液 肾脏 代谢组学 核磁共振 生物标志物 

分 类 号：R-332[医药卫生] R322.61