基于代谢组学的肾苏Ⅱ干预阿霉素肾病小鼠作用机制研究

Metabolomics-based study of Shensu Ⅱ intervention in mouse with adriamycin-induced nephropathy

关键词:  肾苏Ⅱ|代谢组学|肾损伤|生物标记物

Key words:  Shensu Ⅱ|metabolomics|kidney injury|biomarker

摘要:

[目的] 研究肾苏Ⅱ干预阿霉素肾病小鼠的保护作用及对血浆代谢的影响，初步探讨其干预的代谢途径和可能机制。[方法] 通过尾静脉注射阿霉素建立小鼠肾病模型，连续给药14 d后，观察各组小鼠肾脏病理形态学变化；应用超高效液相色谱-飞行时间质谱联用（UPLC-Q-TOF/MS）技术对血浆进行代谢组学研究，筛选并鉴定与肾损伤相关的生物标记物并富集代谢通路，探讨肾苏Ⅱ可能的作用机制。[结果] 肾苏Ⅱ可明显改善注射阿霉素导致肾病小鼠肾组织病理变化；代谢组学分析共筛选到14个潜在生物标志物，涉及氨基酸代谢、胆汁酸代谢、脂质代谢、脂肪酸代谢及嘌呤代谢等过程。[结论] 肾苏Ⅱ能够有效改善阿霉素肾病小鼠损伤，可能通过影响氨基酸代谢、胆汁酸代谢及嘌呤代谢等相关通路发挥作用。

Abstract:

[Objective] To study the protective effect of ShensuⅡintervention on adriamycin-induced nephropathy in mice and its effect on plasma metabolism,and to preliminarily explore the metabolic pathways and possible mechanisms of its intervention.[Methods] A mouse nephropathy model was established by tail vein injection of adriamycin,and the morphological changes of kidney pathology were observed in each group after continuous administration for 14 d. The UPLC-Q-TOF/MS technique was applied to metabolomic study of plasma to screen and identify biomarkers associated with kidney injury and enrich the metabolic pathways to explore the possible mechanism of action of ShensuⅡ.[Results] ShensuⅡsignificantly improved the histopathological changes in the kidney of mice with nephropathy caused by adriamycin injection. The 14 potential biomarkers were screened by metabolomic analysis,involving amino acid metabolism,bile acid metabolism,lipid metabolism,fatty acid metabolism and purine metabolism and other metabolic pathways.[Conclusion] ShensuⅡcan effectively ameliorate the damage in adriamycin nephropathy mice,probably by affecting amino acid metabolism,bile acid metabolism and purine metabolism pathways.