Nephrotic syndrome (NS) is one of the leading causes of end-stage renal failure. Unfortunately, reliable surrogate markers for early diagnosing and monitoring the entire progression of NS are as yet absent. A method using UPLC-Q exactive HR-MS was established for the serum metabolomic study of adriamycin-induced nephropathy in rats. Two rat nephropathy models induced by adriamycin were adopted to reflect different degrees of renal damage of early and advanced stages. Then two MPC5 cell models were used to verify the role of proline in the progression of kidney injury. The results showed that seven metabolites such as 14S-HDHA, DPA, and DHA were associated with early renal injury, while 12 metabolites such as tryptophan, linoleyl carnitine, and LysoPC (18:3) reflected the advanced renal disease. At the same time, metabolites including LPE (22:6), LysoPC (22:5), and proline that changed during the whole process of NS were defined as progressive markers. Pathway analysis results showed that fatty acid metabolism, glycerophospholipid metabolism, and amino acids metabolism participated in the occurrence and development of NS. In addition, the change trend of intracellular proline content was consistent with that in serum, and the results were further supported by the detection of the crucial gene PYCRL. This study provides an important basis for searching for diagnostic markers of NS and also provides a methodological reference for early diagnosing and monitoring the pathogenesis of other progressive diseases.

中文翻译：

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基于血清代谢组学和脯氨酸标记物评估大鼠阿霉素肾病的损伤程度。

肾病综合征（NS）是终末期肾衰竭的主要原因之一。不幸的是，至今还没有用于早期诊断和监测NS整个进程的可靠替代标记。建立了一种使用UPLC-Q精确HR-MS的方法，用于大鼠阿霉素肾病的血清代谢组学研究。采用两种由阿霉素诱导的大鼠肾病模型来反映早期和晚期肾损害的不同程度。然后，使用两个MPC5细胞模型来验证脯氨酸在肾脏损伤进展中的作用。结果显示，14S-HDHA，DPA和DHA等7种代谢物与早期肾损伤有关，色氨酸，亚油酰基肉碱和LysoPC（18：3）等12种代谢物反映了晚期肾脏疾病。同时，代谢产物包括LPE（22：6），LysoPC（22：5）和在整个NS过程中发生变化的脯氨酸被定义为进行性标志物。途径分析结果表明，脂肪酸代谢，甘油磷脂代谢和氨基酸代谢参与了NS的发生和发展。另外，细胞内脯氨酸含量的变化趋势与血清中的趋势一致，关键基因PYCRL的检测进一步支持了这一结果。该研究为寻找NS的诊断标志物提供了重要依据，也为早期诊断和监测其他进行性疾病的发病机理提供了方法学参考。甘油磷脂代谢和氨基酸代谢参与了NS的发生和发展。另外，细胞内脯氨酸含量的变化趋势与血清中的趋势一致，关键基因PYCRL的检测进一步支持了这一结果。该研究为寻找NS的诊断标志物提供了重要依据，也为早期诊断和监测其他进行性疾病的发病机理提供了方法学参考。甘油磷脂代谢和氨基酸代谢参与了NS的发生和发展。另外，细胞内脯氨酸含量的变化趋势与血清中的趋势一致，关键基因PYCRL的检测进一步支持了这一结果。该研究为寻找NS的诊断标志物提供了重要依据，也为早期诊断和监测其他进行性疾病的发病机理提供了方法学参考。