富二十二碳六烯酸-磷脂酰丝氨酸缓解环磷酰胺导致的小鼠肾损伤机制OA北大核心CSTPCD

Objective:To investigate the protective effect and mechanism of docosahexaenoic acid-enriched phosphatidyl serine(DHA-PS)against cyclophosphamide(CTX)-induced renal injury in mice.Methods:Thirty-two male institute of cancer research(ICR)mice were randomly divided into four groups:control(CON),model(MOD),50 mg/kg mb DHA-PS(50 DHA-PS),and 100 mg/kg mb DHA-PS(100 DHA-PS),with eight mice in each group.The renal injury model was established by intraperitoneal injection of 80 mg/kg mb CTX.Five days later,the mice in the MOD and DHA-PS groups were gavaged for 7 days with an equal volume of physiological saline and DHA-PS,respectively and then sacrificed.Kidney indexes,serum biochemical indicators,the levels of renal oxidative stress and inflammatory factors,histopathological changes,and non-targeted metabolomics of renal tissues were evaluated.Results:Compared with the MOD group,DHA-PS significantly decreased kidney indexes,creatinine,blood urea nitrogen,cystatin C,and kidney injury molecule-1 levels(P＜0.05),increased the activities of antioxidant enzymes such as superoxide dismutase(SOD),glutathione peroxidase(GSH-Px),and catalase(CAT)(P＜0.05),reduced the content of malondialdehyde(MDA)(P＜0.05),downregulated the expression of pro-inflammatory cytokines including interleukin(IL)-6,IL-1β,tumor necrosis factor-α(P＜0.05),and upregulated the level of the anti-inflammatory cytokine IL-10(P＜0.05).Staining results showed a significant restoration of kidney tissue structure in the DHA-PS group.Additionally,the results of renal tissue metabolomics indicated that DHA-PS mitigated CTX-induced metabolic disorders in mouse kidneys mainly by affecting glycerophospholipid metabolism,purine metabolism,and their metabolites.Conclusion:DHA-PS can alleviate CTX-induced renal injury in mice through reducing oxidative stress and inflammatory response,and regulating the glycerophospholipid and purine metabolism pathways.