基于液相质谱技术探讨真武汤对阿霉素诱导的扩张型心肌病大鼠血浆代谢物的影响

Effects of Zhenwu Decoction(真武汤) on Plasma Metablites of Rats with Adriamycin-induced Dilated Cardiomyopathy via Liquid Chromatography-mass Spectrometry

目的应用液相质谱代谢组学技术研究阿霉素诱导扩张型心肌病大鼠血浆中代谢物变化以及潜在代谢通路,评价真武汤对代谢物的影响,探讨其治疗扩张型心肌病的作用机制。方法利用阿霉素诱导出大鼠扩张型心肌病模型,采用液相质谱技术结合多元统计分析方法,研究扩张型心肌病大鼠血浆代谢物的变化,并构建潜在的代谢通路。结果在扩张型心肌病大鼠血浆样本中筛选出7种代谢物,与对照组比较,模型组丙酮酸、谷氨酸、L-脯氨酸、羟脯氨酸水平显著降低(P<0.05),L-精氨酸、胸腺嘧啶、胸腺嘧啶脱氧核苷水平显著升高(P<0.05)。与模型组比较,真武汤回调丙酮酸、L-脯氨酸、羟脯氨酸、胸腺嘧啶、胸腺嘧啶脱氧核苷水平,显著升高L-精氨酸水平,对谷氨酸无影响。结论真武汤可能通过调控氨基酸代谢、丙酮酸代谢和核苷代谢等途径治疗扩张型心肌病。

Objective The changes of metabolites and potential pathway of Zhenwu Decoction(真武汤)for rats with adriamycin-induced dilated cardiomyopathy(DCM)were detected by LC-MS.The mechanism in the effects of Zhenwu Decoction on DCM was explored in our study.Methods DCM model was established by using adriamycin.LC-MS was used to detect the changes of plasma metabolites in normal,DCM and Zhenwu Decoction groups.With the differential metabolites,a possible pathway was constructed.Results Seven differential metabolites were picked out in DCM group.Compared with those of the control group,Glutamate,L-proline,Hydroxyproline and Pyruvic acid were down-regulated while L-Arginine,Thymidine and Thymine were up-regulated.Zhenwu Decoction significantly increased the levels of L-proline,Hydroxyproline,L-Arginine and pyruvic acid,whereas reduced the levels of Thymidine and Thymine.It had no effect on Glutamate.Conclusion It is showed that the mechanism of Zhenwu Decoction may be related with amino acid mechanism,pyruvic acid mechanism and nucleoside metabolism.