基于代谢组学的阿霉素肾病大鼠模型损伤程度评价  

Evaluation of injury degree of rat nephropathy model induced by doxorubicin based on metabolomics

作　　者：张王宁 李爱平 刘少博 李科 秦雪梅 

机构地区：[1]地产中药功效物质研究与利用山西省重点实验室,山西省科技创新重点团队,山西太原030006

出　　处：《中草药》2018年第2期360-367,共8页Chinese Traditional and Herbal Drugs

基　　金：国家自然科学基金资助项目(31570346);黄芪生长年限与化学成分积累规律研究(201605D211030);山西省中药产业重点科技攻关项目：道地药材种质资源与规范化生产技术研究(201603D311101);山西省药材行业标准.恒山黄芪药材与精品饮片商品等级标准研究(2014ZD0401)

摘　　要：目的以代谢组学技术对阿霉素肾病大鼠模型损伤程度进行量化分析。方法采用1H-NMR代谢组学技术,结合数理统计方法对不同给药剂量、给药次数的阿霉素肾病大鼠血清样本进行分析,鉴定反映肾病进程的进展性标志物,并依据相关标志物的变化率对肾脏损伤程度进行评价。结果最终得到9个潜在的病理标志物,分别为含氧异己酸、异亮氨酸、亮氨酸、缬氨酸、丙酮酸、3-羟基丁酸、柠檬酸、肌酐和肉毒碱;其中含氧异己酸和肉毒碱存在一定的剂量依赖性,即阿霉素造模剂量越大,这些内源性代谢物的变异越大,表明肾脏损伤越严重,可作为反映肾病进程的进展性标志物。结论这一研究为肾病提供了诊断标志物,为研究其他进展性疾病的发病进程及早期诊断标志物的发现提供研究方法和思路。Objective To carry out the quantitative analysis of the injury degree of model rat ofdoxorubicin-induced nephropathy based on metabolomics. Methods ^1H-NMR based metabolomics approach combined with multivariate statistical analysis were used to analyze rat serum samples from different doses and different times of doxorubicin administration and identify the progressive markers reflecting the progress degree of nephropathy. Moreover, the evaluation of injury degree of rat nephropathy model induced by doxorubicin was conducted according to the change degree of related markers. Results Nine potential biomarkers for pathological conditions were obtained such as 2-oxoisocaproate, isoleucine, leucine, valine, pyruvate, 3-hydroxybutyric acid, citric acid, creatinine, and carnitine, among which 2-oxoisocaproate and carnitine were in a dose-dependent manner, that is, the greater the dose ofdoxorubicin, the greater the variation of the endogenous metabolites, the more severe kidney injury, indicating that 2-oxoisocaproate and carnitine can be used as a progressive markers reflecting the process of kidney disease. Conclusion This study provides the diagnostic marker ofnephropathy, and provides research methods and ideas for the study of other progressive diseases and the discovery of early diagnostic markers.

关 键 词：代谢组学技术 阿霉素 肾病模型 损伤程度 病理标志物 含氧异己酸 异亮氨酸 亮氨酸 缬氨酸 丙酮酸 3-羟基丁酸 柠檬酸 肌酐 肉毒碱 

分 类 号：R965.1[医药卫生—药理学]