Zou Hai-Miao, Zhang Biao, Xu Xin-Chun, Su Jing, Sun Ya-Nan, Xue Song, Wang Xiao-Yan, Qiu Ming-Feng
School of Pharmacy, Shanghai Jiao Tong University, Shanghai 200240, China; School of Pharmacy, Shandong Wanjie Medical Institute, Zibo 255213, China.
School of Pharmacy, Shanghai Jiao Tong University, Shanghai 200240, China.
J Pharm Biomed Anal. 2015 Aug 10;112:98-105. doi: 10.1016/j.jpba.2015.04.033. Epub 2015 Apr 30.
Compound Danshen Dripping Pill (CDDP) has been used for the treatment of coronary heart disease for decades. We aimed to increase the understanding of the mechanisms by evaluating the urinary metabolomics of CDDP using Gas Chromatography-Mass Spectrometer (GC-MS) in a myocardial ischaemia (MI) rat model. One hundred Sprague-Dawley rats were divided into Con (normal saline and no surgery), Con+ (107 mg/kg d CDDP solution and no surgery), Sham (normal saline and surgery without aorta ligation), Mod (normal saline and surgery with aorta ligation), and Mod+ (107 mg/kg d CDDP solution and surgery with aorta ligation) groups. Urine samples on days 0, 3, 14, and 28 were tested using GC-MS and analyzed with PCA and partial least squares-discriminant analysis models. In the Mod group, creatine kinase and malondialdehyde levels were higher, and superoxide-dismutase levels were lower; the same variables normalized in the Mod+ group. CDDP resulted in improvement in the Mod+ group, as indicated by the reduced necrosis in the myocardial tissue. A total of 36 metabolites were identified in the urine samples, and 8 metabolites (malate, succinate, creatinine, methionine, cysteine, serine, phenylalanine, and tyrosine) were increased remarkably and recovered to normal levels after treatment with CDDP. Differentially expressed metabolites implied that energy, amino acid, fatty acid, and polyol metabolism might be disrupted by MI and reversed by CDDP. Urinary metabolomics provide a dynamic monitoring approach that highlights interference by MI and the therapeutic effects of CDDP on MI in rats throughout the recovery process.
复方丹参滴丸(CDDP)已用于治疗冠心病数十年。我们旨在通过在心肌缺血(MI)大鼠模型中使用气相色谱 - 质谱仪(GC - MS)评估CDDP的尿液代谢组学,以加深对其作用机制的理解。将100只Sprague - Dawley大鼠分为Con组(生理盐水且未手术)、Con +组(107 mg/kg d CDDP溶液且未手术)、假手术组(生理盐水且手术但未结扎主动脉)、模型组(生理盐水且手术结扎主动脉)和模型 +组(107 mg/kg d CDDP溶液且手术结扎主动脉)。在第0、3、14和28天采集尿液样本,使用GC - MS进行检测,并通过主成分分析(PCA)和偏最小二乘判别分析模型进行分析。在模型组中,肌酸激酶和丙二醛水平较高,超氧化物歧化酶水平较低;在模型 +组中这些变量恢复正常。CDDP使模型 +组得到改善,表现为心肌组织坏死减少。在尿液样本中总共鉴定出36种代谢物,8种代谢物(苹果酸、琥珀酸、肌酐、蛋氨酸、半胱氨酸、丝氨酸、苯丙氨酸和酪氨酸)显著增加,并在CDDP治疗后恢复到正常水平。差异表达的代谢物表明能量、氨基酸、脂肪酸和多元醇代谢可能因MI而受到干扰,并被CDDP逆转。尿液代谢组学提供了一种动态监测方法,突出了MI的干扰以及CDDP对大鼠MI在整个恢复过程中的治疗效果。