Dysregulation in lipid metabolism is the leading cause of chronic kidney disease (CKD) and also the important risk factors for high morbidity and mortality. Although lipid abnormalities were identified in CKD, integral metabolic pathways for specific individual lipid species remain to be clarified. We conducted ultra-high-performance liquid chromatography-high-definition mass spectrometry-based lipidomics and identified plasma lipid species and therapeutic effects of Rheum officinale in CKD rats. Adenine-induced CKD rats were administered Rheum officinale. Urine, blood and kidney tissues were collected for analyses. We showed that exogenous adenine consumption led to declining kidney function in rats. Compared with control rats, a panel of differential plasma lipid species in CKD rats was identified in both positive and negative ion modes. Among the 50 lipid species, phosphatidylcholine (PC), lysophosphatidylcholine (LysoPC) and lysophosphatidic acid (LysoPA) accounted for the largest number of identified metabolites. We revealed that six PCs had integral metabolic pathways, in which PC was hydrolysed into LysoPC, and then converted to LysoPA, which was associated with increased cytosolic phospholipase A₂ protein expression in CKD rats. The lower levels of six PCs and their corresponding metabolites could discriminate CKD rats from control rats. Receiver operating characteristic curves showed that each individual lipid species had high values of area under curve, sensitivity and specificity. Administration of Rheum officinale significantly improved impaired kidney function and aberrant PC metabolism in CKD rats. Taken together, this study demonstrates that CKD leads to PC metabolism disorders and that the dysregulation of PC metabolism is involved in CKD pathology.

脂质代谢失调是慢性肾脏病（CKD）的主要原因，也是高发病率和死亡率的重要危险因素。尽管在 CKD 中发现了脂质异常，但特定个体脂质种类的整体代谢途径仍有待阐明。我们进行了基于超高效液相色谱-高清质谱的脂质组学，并鉴定了大黄对 CKD 大鼠的血浆脂质种类和治疗作用。腺嘌呤诱导的 CKD 大鼠服用大黄。收集尿液、血液和肾组织进行分析。我们发现外源性腺嘌呤消耗导致大鼠肾功能下降。与对照大鼠相比，在正离子和负离子模式下都鉴定出 CKD 大鼠的一组差异血浆脂质种类。在 50 种脂质中，磷脂酰胆碱 (PC)、溶血磷脂酰胆碱 (LysoPC) 和溶血磷脂酸 (LysoPA) 占已鉴定代谢物的数量最多。我们发现 6 个 PC 具有完整的代谢途径，其中 PC 被水解为 LysoPC，然后转化为 LysoPA，这与 CKD 大鼠中胞浆磷脂酶 A ₂蛋白表达增加有关。六种 PC 及其相应代谢物的较低水平可以将 CKD 大鼠与对照大鼠区分开来。受试者工作特征曲线显示，每种脂质均具有较高的曲线下面积、敏感性和特异性。服用大黄可显着改善 CKD 大鼠肾功能受损和 PC 代谢异常。 综上所述，本研究表明 CKD 会导致 PC 代谢紊乱，并且 PC 代谢失调与 CKD 病理有关。