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[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
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[Abstract]
Objective To carry out the quantitative analysis of the injury degree of model rat of doxorubicin-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 of doxorubicin, 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 of nephropathy, and provides research methods and ideas for the study of other progressive diseases and the discovery of early diagnostic markers.
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[基金项目]
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)