基于UPLC-Q/TOF-MS技术探讨抗纤益心方干预扩张型心肌病的作用机制  

Mechanism of Kangxian Yixin Decoction on dilated cardiomyopathy based on UPLC-Q/TOF-MS

作　　者：李巧稚 郭宗耀 王振涛[2] 吴鸿[1] LI Qiao-zhi;GUO Zong-yao;WANG Zhen-tao;WU Hong(Henan University of Chinese Medicine,Zhengzhou 450046,China;Department of Cardiology,Henan Province Hospital of TCM,Zhengzhou 450002,China)

机构地区：[1]河南中医药大学,郑州450046 [2]河南省中医院心病科,郑州450002

出　　处：《中华中医药杂志》2022年第5期2916-2923,共8页China Journal of Traditional Chinese Medicine and Pharmacy

基　　金：国家自然科学基金面上项目(No.81573920)。

摘　　要：目的:运用UPLC-Q/TOF-MS技术筛选抗纤益心方干预扩张型心肌病(DCM)的差异代谢物,探讨抗纤益心方(KXYX)干预DCM的作用机制。方法:建立呋喃唑酮诱导的DCM大鼠模型,造模成功的大鼠随机分为模型组和KXYX组,KXYX组给予KXYX颗粒剂灌胃治疗4周,超声心动图检测大鼠心脏结构和心功能,取心肌组织观察病理变化,应用UPLC-Q/TOF-MS技术提取心肌组织样品中的代谢物,筛选差异代谢物,找出潜在生物标记物。同时,通过KEGG通路富集分析得到差异代谢物参与的代谢通路。结果:超声心动图示KXYX组大鼠LVEDD、LVESD显著缩短,LVEF显著升高(P<0.05)。HE、Masson染色示KXYX组大鼠心肌病理损害及胶原纤维的异常增生被抑制。KXYX组与模型组相比得到140个差异代谢物,其中112个表达上调,28个表达下调。与模型组比较,KXYX组中己二酸、亚油酸、2’-甲氧基胞苷、左旋肉碱等具有明显回调。对差异代谢物综合分析显示,KXYX治疗DCM主要通过调节氨基酸合成与代谢、嘌呤代谢、硫代谢等途径。结论:KXYX可能通过调节心肌组织的15种潜在生物标志物及差异蛋白相关的代谢通路干预DCM治疗,作用机制可能为调节能量代谢、氨基酸合成与代谢、嘌呤代谢、胆固醇代谢、硫代谢、亚油酸代谢等途径。Objective:To screen the differential metabolites of Kangxian Yixin Decoction(KXYX)in the intervention of dilated cardiomyopathy(DCM)by UPLC-Q/TOF-MS,and to explore the mechanism of KXYX in the intervention of DCM.Methods:The rat model of DCM induced by furazolidone was established.The successful model rats were randomly divided into model group and KXYX group.KXYX group was given KXYX granules by gavage for 4 weeks.Echocardiography was used to detect cardiac structure and cardiac function in rats.Myocardial tissue was taken to detect pathological changes.UPLC-Q/TOF-MS technology was used to extract metabolites in myocardial tissue samples,screen differential metabolites and identify potential biomarkers.At the same time,the metabolic pathways involved in different metabolites were obtained by KEGG pathway enrichment analysis.Results:Echocardiography showed that LVEDD and LVESD in the KXYX group were significantly shortened,and LVEF was significantly increased(P<0.05).HE staining and Masson staining showed that the myocardial pathological damage and the abnormal proliferation of collagen fibers in the KXYX group were inhibited.Compared with the model group,140 differential metabolites were obtained in KXYX group,of which 112 were up-regulated and 28 were down-regulated.Adipic acid,linoleic acid,2’-methoxycytidine and L-carnitine in the KXYX group had obvious correction.The comprehensive analysis of differential metabolites showed that KXYX in the treatment of DCM mainly regulated amino acid synthesis and metabolism,purine metabolism and sulfur metabolism.Conclusion:The treatment of DCM with KXYX may be achieved by regulating 15 potential biomarkers and differential protein-related metabolic pathways in myocardial tissue,and it is related to regulating energy metabolism,amino acid synthesis and metabolism,purine metabolism,cholesterol metabolism,sulfur metabolism,linoleic acid metabolism and other pathways.

关 键 词：代谢组学 扩张型心肌病 抗纤益心方 差异代谢物 生物标记物 代谢通路 

分 类 号：R285.5[医药卫生—中药学]