Protective effect of Qifu decoction on adriamycin-induced cardiac injury based on GC-MS serum metabolomics
-
摘要: 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。Abstract: 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.
-
Key words:
- adriamycin /
- cardio-toxicity /
- Qifu decoction /
- metabolomics /
- GC-MS
-
[1] BROWN SA, SANDHU N, HERRMANN J. Systems biology approaches to adverse drug effects:the example of cardio-oncology[J]. Nat Rev Clin Oncol,2015, 12(12):718-731. [2] 于彩娜, 范颖, 林庶茹. 芪附汤对阿霉素心脏毒性损伤的保护作用及其抗氧化机制[J]. 中国实验方剂学杂志,2011,17(8):193-196. [3] 于彩娜, 范颖, 林庶茹. 芪附汤抑制阿霉素心脏毒性损伤大鼠心肌细胞凋亡的研究[J]. 中国实验方剂学杂志,2011,17(15):148-151. [4] 范颖, 才丽平, 于彩娜, 等. 参附汤、芪附汤、姜附汤对阿霉素心脏毒性损伤大鼠线粒体途径细胞凋亡的影响[J]. 中国实验方剂学杂志,2010,16(8):135-138. [5] FESSENDEN M. Metabolomics:small molecules, single cells[J]. Nature,2016, 540(7631):153-155. [6] TAN G, LIAO W, DONG X, et al. Metabonomic profiles delineate the effect of Traditional Chinese Medicine sini decoction on myocardial infarction in rats[J]. PLoS ONE,2012, 7(4):e34157. [7] SMITH CA, WANT EJ, O'MAILLE G, et al. XCMS:processing mass spectrometry data for metabolite profiling using nonlinear peak alignment, matching, and identification[J]. Anal Chem,2006, 78(3):779-787. [8] XIA J, WISHART DS. Using metaboanalyst 3.0 for comprehensive metabolomics data analysis[J]. Curr Protoc Bioinformatics,2016, 55(1):14.10.1-14.10.91. [9] GIKA HG, THEODORIDIS GA, WINGATE JE, et al. Within-day reproducibility of an HPLC-MS-based method for metabonomic analysis:application to human urine[J]. J Proteome Res,2007, 6(8):3291-3303. -
点击查看大图
计量
- 文章访问数: 2856
- HTML全文浏览量: 394
- PDF下载量: 524
- 被引次数: 0
下载:
