School of Pharmacy, Zhejiang Chinese Medical University, No. 548 Binwen Road, Hangzhou, 310053, China.
Faculty of Life Science & Medicine, Northwest University, No. 229 Taibai North Road, Xi'an, 710069, China.
Acta Pharmacol Sin. 2023 Feb;44(2):393-405. doi: 10.1038/s41401-022-00947-x. Epub 2022 Aug 3.
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 A 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 中已经发现了脂质异常，但特定个体脂质种类的完整代谢途径仍有待阐明。我们进行了基于超高效液相色谱-高分辨率质谱的脂质组学研究，鉴定了血浆脂质种类和大黄在 CKD 大鼠中的治疗作用。腺嘌呤诱导的 CKD 大鼠给予大黄治疗。收集尿液、血液和肾脏组织进行分析。结果显示，外源性腺嘌呤的摄入导致大鼠肾功能下降。与对照组大鼠相比，在 CKD 大鼠的正离子和负离子模式下均鉴定出一组差异表达的血浆脂质种类。在 50 种脂质种类中，磷脂酰胆碱（PC）、溶血磷脂酰胆碱（LysoPC）和溶血磷脂酸（LysoPA）占鉴定出的代谢物的最大数量。我们揭示了六个 PC 具有完整的代谢途径，其中 PC 水解成 LysoPC，然后转化为 LysoPA，这与 CKD 大鼠细胞质磷脂酶 A 蛋白表达增加有关。六个 PC 及其相应代谢物的水平降低可以将 CKD 大鼠与对照组大鼠区分开来。受试者工作特征曲线显示，每个个体脂质种类的曲线下面积、灵敏度和特异性均具有较高的值。大黄治疗显著改善了 CKD 大鼠受损的肾功能和异常的 PC 代谢。总之，这项研究表明 CKD 导致 PC 代谢紊乱，PC 代谢失调参与了 CKD 发病机制。
