Study on the mechanism of Amygdalus mongolica oil anti-renal fibrosis based on metabolomics and transcriptomics

Abstract

Renal fibrosis (RF) precedes all kidney diseases, and eventually progresses to end-stage renal failure. It is one of the main pathological manifestations of chronic kidney disease (CKD), which seriously affects the patients’ quality of life. The oil from the seeds of Amygdalus mongolica has been shown to prevent RF in rats, although the mechanism of action is still unclear. The aim of this study was to elucidate the mechanisms underlying the reno-protective effect of A. mongolica oil in a rat model using metabolomics and transcriptomics. Here, RF was induced by unilateral ureteral obstruction (UUO), and the animals were treated with A. mongolica oil (7.5, 5.0, 2.5 ml/kg). Kidney function was evaluated in terms of serum creatinine (Scr), blood urea nitrogen (BUN), albumin (ALB), hydroxyproline (HYP), malondialdehyde (MDA) and superoxide dismutase (SOD) levels. LC-MS/MS was used for urine metabolomics and transcriptomic analysis of renal tissues was performed by RNA-Seq. The results showed that A. mongolica oil significantly reduced the levels of Scr, BUN, HYP and MDA, and increased that of SOD. In addition, the animals treated with the oil showed partial improvement in renal fibrosis and tissue damage. Metabolomics and transcriptomics identified lysine degradation and purine metabolism as the two key pathways involved in RF. Furthermore, 5 metabolic biomarkers including saccharopine, 2-oxoadipic acid, pipecolic acid, allantoic acid and uric acid, and 4 differentially expressed genes (Prdm6, Ampd1, Pde6g, Nt5c) were mapped by these pathways, and may be potential therapeutic targets. A. mongolica oil reduced the levels of the above metabolites, downregulated Prdm6, and upregulated Ampd1. Therefore, A. mongolica likely exerts its anti-fibrotic effects by targeting lysine degradation and purine metabolism in the kidneys. This study is the first to elucidate the metabolic basis of the reno-protective effects of A. mongolica oil, and provides novel insights into its molecular mechanisms.