参麦方对于大鼠心肌损伤保护作用的代谢组学研究

摘要

目的：运用代谢组学方法研究参麦方对于由阿霉素所造成的大鼠心肌损伤的保护作用，探讨参麦方在体内发挥药效的作用机制。方法通过超高效液相色谱-飞行时间质谱( UPLC/TOF-MS)分析药物作用后大鼠尿液的代谢物图谱，采用偏最小二乘法判别分析( PLS-DA)和正交偏最小二乘法判别分析( OPLS-DA)寻找各组代谢物差异，变量重要性投影( VIP)及t检验筛选潜在内源性标志物。结果鉴定出琥珀酰腺苷、环磷酸腺苷、S-三甲基丁酰基二氢硫辛酰胺、4-羟基环氧乙酸、苯丁酰谷氨酰胺、丁酸甲酯、3-羟基十四烯二酸、二氢硫辛酰胺、丙酮酸等14种内源性代谢物。结论参麦方可通过调节嘌呤代谢、部分氨基酸代谢、脂肪代谢和能量代谢等来发挥保护心肌损伤的作用。该研究解释了参麦方在体内发挥药效的作用机制，为两药配伍的合理性及临床联合用药治疗疾病提供了理论依据。%Aim With metabolomics method, to study Shen-Mai decoction’ s function on protecting the myo-cardial injured rats caused by doxorubicin for probing into the functioning mechanism of Shen-Mai decoction’ s medical effect. Methods By means of UPLC-TOF-MS, the metabolites of urine of the rats treated by Shen-Mai decoction were analyzed. Then, the differ-ences between each group of the metabolites were sought with PLS-DA ( the partial least square discrimi-nant analysis ) and OPLS-DA ( the orthogonal partial least squares discriminant analysis ) . VIP ( variable importance in projection ) and t test were used to screen out potential biomarkers. Results Fourteen endogenous metabolites such as succinyladenosine, a-denosine 2′, 3′-cyclic phosphate, S-( 3-methylbu-tanoyl )-dihydrolipoamide-E, cis-4-hydroxycyclohexy-lacetic acid, phenylbutyrylglutamine, 3-butyn-1-al, 3-hydroxytetradecanedioic acid, dihydrolipoamide and pyruvic acid, etc. were characterized. Conclusions The results indicate that Shen-Mai decoction can pro-tect the body from myocardial injury by regulating pu-rine metabolism, some acid metabolism, fat metabo-lism and energy metabolism, etc. The study expounds the functioning mechanism for Shen-Mai decoction ’ s medical effect in the body and provides theoretical grounds for the rationality of the two medical herbs ’ compatibility and their combination in clinical treat-ment of diseases.