Jian Wei-Xiong, Chen Qing-Hua, Huang Xian-Ping
Diagnostic Institute of Traditional Chinese Medicine, Physiopathological Laboratory of State Administration of Traditional Chinese Medicine, Hunan University of Traditional Chinese Medicine, Changsha 410007.
Zhongguo Zhong Xi Yi Jie He Za Zhi. 2012 Apr;32(4):515-20.
To find out the metabolite profile of rats' myocardial tissue of cardiac blood stasis syndrome (CBSS), and to analyze the metabolic pathway of CBSS rats' myocardial tissue by observing the changes of phenotypes intervened by Yangxin Tongmai Recipe (YTR).
Acute myocardial infarction (AMI) rat model of CBSS was prepared by ligating the left anterior descending coronary artery. Meanwhile, the model was interfered with YTR. The metabolites of rats' myocardial tissue were detected in the model group, the YTR group, the sham-operation group, and the blank control group using GC-MS (8 rats in each group). Changes of metabolite contents were analyzed among different groups using principal component analysis (PCA) and least-square analysis.
As for PCA: The results of PCA showed that principal component integral (PCI) of the four groups was mainly distributed in the three regions of oval scatterplot. The factor loading gram showed that contents of glycine, fumaric acid, malic acid, glutamic acid, glucose, phosphoric acid, galactopyranose, lysine were changed in the model group. Analysis of partial least square method: PLS regression model showed that obvious linear correlation existed between the model group and the YTR group, which proved the model was reasonably established. The drug intervention was highly positively correlated with glycine, malic acid, glutamic acid, glucose, highly correlated with urea and butanedioic acid, but negatively correlated with lysine. According to VIP value, each variable was closely correlated with the drug intervention in sequence as malic acid, glutamic acid, glycine, glucose, fumaric acid, urea, galactose, tyrosine, lactic acid, and alanine. Results of variability analysis: Obvious changed variability analysis of metabolite difference showed that 10 metabolites such as glycine, etc. obviously decreased in the model group, showing significant difference when compared with the normal group (P<0.01). Compared with the model group, contents of glycine, fumaric acid, malic acid, glutamic acid, glucose, tyrosine,urea, lactic acid, and alanine, etc. obviously increased after drug intervention (P<0.01). Of them, the increment of malic acid, glumatic acid, tyrosine, and urea was less, showing significant difference when compared with that of the normal group. The mean of lysine was slightly lowered after drug intervention, but with insignificant difference when compared with that of the model group. AMI rats of CBSS was closely correlated with myocardial metabolites such as malic acid, glutamic acid, glycine, glucose, fumaric acid, urea, galactopyranose, lactic acid, alanine, and tyrosine, etc.
The metabolite profile of rats' myocardial tissue showed AMI rat model of CBSS was closely correlated with post-hypoxia glucose metabolism disorder. YTR could effectively intervene this process.
探寻心血瘀阻证(CBSS)大鼠心肌组织的代谢物谱,并通过观察养心通脉方(YTR)干预后表型的变化,分析CBSS大鼠心肌组织的代谢途径。
采用结扎冠状动脉左前降支的方法制备CBSS急性心肌梗死(AMI)大鼠模型。同时,用YTR对模型进行干预。运用气相色谱 - 质谱联用技术(GC - MS)检测模型组、YTR组、假手术组和空白对照组大鼠心肌组织的代谢物(每组8只大鼠)。采用主成分分析(PCA)和最小二乘法分析不同组间代谢物含量的变化。
关于PCA:PCA结果显示,四组的主成分积分(PCI)主要分布在椭圆形散点图的三个区域。因子载荷图显示,模型组中甘氨酸、富马酸、苹果酸、谷氨酸、葡萄糖、磷酸、吡喃半乳糖、赖氨酸的含量发生了变化。偏最小二乘法分析:PLS回归模型显示模型组与YTR组之间存在明显的线性相关性,证明模型构建合理。药物干预与甘氨酸、苹果酸、谷氨酸、葡萄糖呈高度正相关,与尿素和丁二酸呈高度相关,但与赖氨酸呈负相关。根据VIP值,各变量与药物干预的密切程度依次为苹果酸、谷氨酸、甘氨酸、葡萄糖、富马酸、尿素、半乳糖、酪氨酸、乳酸、丙氨酸。变异性分析结果:代谢物差异的变异性分析显示,模型组中甘氨酸等10种代谢物明显降低,与正常组相比差异有统计学意义(P<0.01)。与模型组相比,药物干预后甘氨酸、富马酸、苹果酸、谷氨酸、葡萄糖、酪氨酸、尿素、乳酸、丙氨酸等的含量明显增加(P<0.01)。其中,苹果酸、谷氨酸、酪氨酸和尿素的增加幅度较小,与正常组相比差异有统计学意义。药物干预后赖氨酸的平均值略有降低,但与模型组相比差异无统计学意义。CBSS的AMI大鼠与苹果酸、谷氨酸、甘氨酸、葡萄糖、富马酸、尿素、吡喃半乳糖、乳酸、丙氨酸、酪氨酸等心肌代谢物密切相关。
大鼠心肌组织的代谢物谱表明,CBSS的AMI大鼠模型与缺氧后糖代谢紊乱密切相关。YTR可有效干预这一过程。