芪附汤对大鼠抗阿霉素心脏毒性作用的血清气相色谱-质谱代谢组学研究

Protective effect of Qifu decoction on adriamycin-induced cardiac injury based on GC-MS serum metabolomics

目的采用基于气相色谱-质谱(GC-MS)血清代谢组学技术研究芪附汤抗阿霉素心脏毒性的作用,并初步探讨其作用机制。方法将24只大鼠分为正常组、阿霉素组和芪附汤治疗组,给予4周相应的干预治疗后,采集大鼠血清进行GC-MS分析,结合多变量和单变量统计分析,研究阿霉素诱导的心脏毒性损伤大鼠血清中内源性代谢物的变化,以及芪附汤对其的干预作用,寻找其抗阿霉素心脏毒性潜在的生物标志物,采用代谢通路分析鉴定芪附汤靶向代谢通路。结果 GC-MS血清代谢组学分析鉴定了17种阿霉素心脏毒性潜在生物标志物,芪附汤对其中10种代谢物具有显著的逆转作用,代谢通路分析表明,三羧酸循环、乙醛酸和二羧酸代谢(简称二羧酸代谢)、花生四烯酸代谢是芪附汤主要的靶向代谢通路。结论芪附汤能够通过调节失衡的三羧酸循环、二羧酸代谢和花生四烯酸代谢而发挥抗阿霉素心脏毒性的作用。

Objective To evaluate the protective effect of Qifu decoction（QFD）on adriamycin-induced cardiac injury based on GC-MS serum metabolomics and explore its mechanism.Methods Twenty-four rats were randomly divided into three groups：control group,Adriamycin-induced model group and QFD-treated group.The QFD-treated group received QFD for 4 weeks.After 4 weeks,the serum samples of each rat were collected and analyzed by GC-MS.Combination GC-MS with multivariate and univariate statistical analysis was applied to identify potential biomarkers related with adriamycin-induced cardiac injury and QFD-reversed biomarkers.Metabolic pathway analysis was employed to identify QFD-targeted metabolic pathways.Results 17 metabolites were identified as potential biomarkers related with adriamycin-induced cardiac injury based on GC-MS serum metabolomics analysis and 10 metabolites were significantly reversed by QFD.QFD-targeted metabolic pathways were identified by metabolic pathway analysis with MetaboAnalyst,which were citrate cycle,glyoxylate and dicarboxylate metabolism and arachidonic acid metabolism.Conclusion QFD administration provided protective effects on adriamycin-induced cardiac injury through partially regulating the perturbed citrate cycle,glyoxylate and dicarboxylate metabolism and arachidonic acid metabolism.