基于非靶向尿液代谢组学技术的毛蕊花糖苷治疗嘌呤霉素氨基核苷肾病幼龄大鼠相关生物标志物研究  

Study on biomarkers of acteoside in treating puromycin aminonucleoside nephropathy in young rats based on non-targeted urine metabolomics technology

作　　者：王梦晓 罗珂珂 高文雅 田孟尧 赵海誉[1] 司南[1] 边宝林[1] 魏晓露[1] 王宏洁[1] 周严严[1] WANG Meng-xiao;LUO Ke-ke;GAO Wen-ya;TIAN Meng-yao;ZHAO Hai-yu;SI Nan;BIAN Bao-lin;WEI Xiao-lu;WANG Hong-jie;ZHOU Yan-yan(Institute of Chinese Materia Medica,China Academy of Chinese Medical Sciences,Beijing 100700,China)

机构地区：[1]中国中医科学院中药研究所,北京100700

出　　处：《中国中药杂志》2023年第21期5898-5907,共10页China Journal of Chinese Materia Medica

摘　　要：通过非靶向尿液代谢组学技术研究毛蕊花糖苷对嘌呤霉素氨基核苷肾病(purinomycin aminonucleoside nephropathy,PAN)幼龄大鼠的内源性代谢特征,初步探讨其潜在的作用机制。采用全自动生化仪检测各组大鼠尿液生化指标含量;采用超高效液相色谱串联静电场轨道阱高分辨质谱(UHPLC-LTQ-Orbitrap MS)联合主成分分析(principal component analysis,PCA)、正交偏最小二乘法判别分析(orthogonal partial least squares-discrimination analysis,OPLS-DA)等寻找筛选潜在生物标志物及相关核心代谢通路。使用MetaboAnalyst 5.0平台绘制工作特征(receiver operating characteristic,ROC)曲线来评估核心代谢物临床诊断效能。结果显示,毛蕊花糖苷显著降低PAN幼龄大鼠尿蛋白/尿肌酐比值。PAN幼龄大鼠模型非靶向尿液代谢组学共筛选出17种差异代谢物,涉及到的通路有苯丙氨酸代谢以及苯丙氨酸、酪氨酸和色氨酸的生物合成;毛蕊花糖苷干预PAN幼龄大鼠共筛选出13种差异代谢物,涉及到的通路有苯丙氨酸代谢以及精氨酸和脯氨酸代谢,其中,毛蕊花糖苷治疗后可显著回调的差异代谢物有亮氨酰脯氨酸和苯乙酮。这些通路主要揭示了毛蕊花糖苷干预PAN幼龄大鼠的主要作用机制为氨基酸代谢。ROC曲线进一步分析出的2种核心生物标志物亮氨酰脯氨酸和苯乙酮的曲线下面积均大于0.9。综上所述,毛蕊花糖苷可能通过回调内源性差异代谢物调控氨基酸代谢相关通路治疗PAN幼龄大鼠,这将有助于初步阐明毛蕊花糖苷治疗儿童慢性肾小球肾炎的干预机制。同时提取出的特征性生物标志物对于评估毛蕊花糖苷治疗儿童慢性肾小球肾炎具有较高的诊断价值。This study aims to reveal the endogenous metabolic characteristics of acteoside in the young rat model of purinomycin aminonucleoside nephropathy(PAN)by non-targeted urine metabolomics and decipher the potential mechanism of action.Biochemical indicators in the urine of rats from each group were determined by an automatic biochemical analyzer.The potential biomarkers and related core metabolic pathways were identified by ultra-high performance liquid chromatography coupled with linear ion trap-Orbitrap mass spectrometry(UHPLC-LTQ-Orbitrap MS)combined with principal component analysis(PCA)and orthogonal partial least squares-discriminant analysis(OPLS-DA).MetaboAnalyst 5.0 was used to establish the receiver operating characteristic(ROC)curve for evaluating the clinical diagnostic performance of core metabolites.The results showed that acteoside significantly decreased urinary protein-to-creatinine ratio in PAN young rats.A total of 17 differential metabolites were screened out by non-targeted urine metabolomics in PAN young rats and they were involved in phenylalanine metabolism and phenylalanine,tyrosine and tryptophan biosynthesis.Thirtten differential metabolites were screened by acteoside intervention in PAN young rats,and they were involved in phenylalanine metabolism and arginine and proline metabolism.Among them,leucylproline and acetophenone were the differential metabolites that were significantly recovered after acteoside treatment.These pathways suggest that acteoside treats PAN in young rats by regulating amino acid metabolism.The area under the curve of two core biomarkers,leucylproline and acetophenone,were both greater than 0.9.In summary,acteoside may restore amino acid metabolism by regulating endogenous differential metabolites in PAN young rats,which will help to clarify the mechanism of acteoside in treating chronic glomerulonephritis in children.The characteristic biomarkers screened out have a high diagnostic value for evaluating the treatment of chronic glomerulonephritis in children with ac

关 键 词：非靶向尿液代谢组学 嘌呤霉素氨基核苷肾病 毛蕊花糖苷 生物标志物 

分 类 号：R285.5[医药卫生—中药学]