基于1H-NMR代谢组学探讨雷公藤红素改善糖脂代谢紊乱的机制

Exploring mechanism of celastrol in improving glycolipid metabolism disorders based on ~1H-NMR metabolomics

目的:通过^(1)H-NMR代谢组学方法探讨雷公藤红素(CEL)对糖脂代谢紊乱模型小鼠的改善作用和潜在机制。方法:选取32只雄性健康C57BL/6J小鼠,随机分对照组(LFD组)、模型组(HFD组)、对照给药组(LFD+CEL组)和模型给药组(HFD+CEL组),建立高脂饮食诱导糖脂代谢紊乱小鼠模型,10周后LFD+CEL组和HFD+CEL组小鼠腹腔注射CEL(100µg/kg),LFD组和HFD组小鼠腹腔注射等量的溶剂,连续给药6周,检测相关生化指标水平,观察各组小鼠组织病理改变;采用^(1)H-NMR代谢组学方法分析模型小鼠血浆的代谢特征及CEL干预作用。结果:HFD+CEL组小鼠血浆中各生化指标水平与HFD组比较均有显著性差异(P<0.05,P<0.01);肝脏脂肪变性显著改善;糖脂代谢紊乱和血浆代谢特征明显好转;CEL改善模型小鼠糖脂紊乱可能与脂质代谢、肌酸代谢、脂肪酸的β-氧化、三羧酸循环、氨基酸代谢、糖异生和糖酵解等多种代谢途径有关。结论:CEL可通过调节脂质代谢、肌酸代谢、脂肪酸的β-氧化、三羧酸循环、氨基酸代谢、糖异生和糖酵解等多种代谢途径改善高脂诱导的糖脂代谢紊乱。

Objective:To explore the improvement effect and potential mechanism of celastrol(CEL)on glycolipid metabolism disorders in model mice by1H-NMR metabolomics method.Methods:Thirty-two male healthy C57BL/6J mice were randomly divided into control group(LFD group),model group(HFD group),control treatment group(LFD+CEL group),and model treatment group(HFD+CEL group).Mouse models of glycolipid metabolism disorders were induced by a high-fat diet.After 10 weeks,the mice in LFD+CEL group and HFD+CEL group were injected i.p.with CEL(100µg/kg);while those in LFD group and HFD group were injected i.p.with equal amount of solvent,the administration lasted continuously for 6 weeks.The biochemical parameters were detected and histopathological changes of the mice in each group were observed.1H-NMR metabolomics method was applied to analyze the plasma metabolic characteristics and the intervention effect of CEL in model mice.Results:The levels of biochemical parameters of the mice plasma in the HFD+CEL group were significantly different from those in the HFD group(P<0.01,P<0.05).Hepatic steatosis was significantly improved.Glycolipid metabolism disorders and plasma metabolism characteristics were significantly improved.The improvement effect of CEL on glycolipid metabolism disorders in model mice may be related to multiple metabolic pathways,such as lipid metabolism,creatine metabolism,β-oxidation of fatty acids,tricarboxylic acid cycle,amino acid metabolism,gluconeogenesis and glycolysis.Conclusion:CEL may improve high-fat-induced glycolipid metabolism disorders by regulating lipid metabolism,creatine metabolism,β-oxidation of fatty acids,tricarboxylic acid cycle,amino acid metabolism,gluconeogenesis and glycolysis.