参附汤抗阿霉素心肌病小鼠血清代谢组学研究  

Serum metabolomic study of Shenfu decoction on adriamycin-induced cardiomyopathy in mice

作　　者：秦烨 丁欣 张雅 QIN Ye;DIN Xin;ZHANG Ya(The General Hospital of the Central Theater Command of the PLA,Wuhan 430014,China;School of Pharmacy,Air Force Medical University,Xi’an 710032,China;School of Pharmacy,Shaanxi University of Chinese Medicine,Xi’an 712046,China)

机构地区：[1]中国人民解放军中部战区总医院,湖北武汉430014 [2]空军军医大学药学系,陕西西安710032 [3]陕西中医药大学药学院,陕西西安712046

出　　处：《药学实践杂志》2022年第2期108-112,共5页Journal of Pharmaceutical Practice

基　　金：陕西省自然科学基础研究计划(2020JQ-449)。

摘　　要：目的应用血清代谢组学技术,研究参附汤对阿霉素心脏毒性的逆转作用,探讨其作用机制。方法建立阿霉素致心肌病BALB/c小鼠模型,给予相应的干预,测定血清乳酸脱氢酶(LDH)、肌酸磷化酶-同功酶MB(CK-MB);超声心动图测定射血分数(EF)和缩短分数(FS)。采集小鼠血清进行气相色谱-质谱(GC-MS)分析,所得数据经多变量和单变量统计分析,比较正常组、模型组和参附汤治疗组小鼠血清中内源性代谢物的变化,寻找参附汤逆转阿霉素心脏毒性潜在的生物标志物,采用代谢通路分析探讨参附汤靶向代谢通路。结果模型组血清LDH、CK-MB水平明显升高,EF、FS值明显下降,表明造模成功,经参附汤治疗后上述指标显著改善。代谢组学分析鉴定出13种阿霉素对心脏毒性的潜在生物标志物,参附汤对其中11种代谢物具有显著的逆转作用。代谢通路分析表明,苯丙氨酸、酪氨酸和色氨酸的合成、花生四烯酸代谢、苯丙氨酸代谢、三羧酸循环和二羧酸代谢是参附汤主要的靶向代谢通路。结论参附汤能通过调节失衡的苯丙氨酸、酪氨酸和色氨酸的合成,以及花生四烯酸、苯丙氨酸、二羧酸代谢和三羧酸循环发挥逆转阿霉素心脏毒性的作用。Objective To study the reversal effect of Shenfu decoction(SFD)on adriamycin-induced cardiomyopathy and explore its mechanism by using serum metabolomic technology.Methods The BALB/c mouse model of cardiomyopathy induced by adriamycin was established.The corresponding intervention was given.The serum lactate dehydrogenase(LDH)and creatine phosphatase isoenzyme MB(CK-MB)were measured.The ejection fraction(EF)and shortening fraction(FS)were measured by echocardiography.Mouse serum was collected for gas chromatography-mass spectrometry(GC-MS)analysis.The data obtained was analyzed by multivariate and univariate statistical analysis to compare the changes of endogenous metabolites in the serum of mice in the normal group,model group and Shenfu decoction treatment group,to find the potential biomarkers of Shenfu decoction to reverse the adriamycin-induced cardiomyopathy.Metabolic pathway analysis was used to explore the targeted metabolic pathway of Shenfu decoction.Results The levels of serum LDH and CK-MB in the model group were increased significantly,and the values of EF and FS decreased significantly,indicating that the model was successfully established.The above indicators were significantly improved after treatment with Shenfu decoction.13 potential biomarkers of adriamycin-induced cardiomyopathy were identified by metabonomic analysis,and Shenfu decoction had significant reversal effect on 11 metabolites.Metabolic pathway analysis showed that the synthesis of phenylalanine,tyrosine and tryptophan,arachidonic acid metabolism,phenylalanine metabolism,tricarboxylic acid cycle and dicarboxylic acid metabolism were the main targeted metabolic pathways of Shenfu decoction.Conclusion Shenfu decoction can reverse adriamycin-induced cardiomyopathy by regulating the unbalanced synthesis of phenylalanine,tyrosine and tryptophan,as well as the metabolism of arachidonic acid,phenylalanine,dicarboxylic acid and tricarboxylic acid cycle.

关 键 词：阿霉素 心脏毒性 参附汤 代谢组学 气相色谱-质谱 

分 类 号：R978[医药卫生—药品]