Yan Bei, A JiYe, Hao HaiPing, Wang GuangJi, Zhu XuanXuan, Zha WeiBin, Liu LinSheng, Guan EnZe, Zhang Ying, Gu ShengHua, Huang Qing, Zheng YuanTing
Key Laboratory of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Nanjing, China.
Sci China C Life Sci. 2009 Nov;52(11):1081-90. doi: 10.1007/s11427-009-0136-y. Epub 2009 Nov 24.
The traditional Chinese medicine concepts of "Xinxueyuzuzheng (heart blood stasis obstruction pattern)" and "Qiyinliangxuzheng (qi and yin deficiency pattern)" for myocardial ischemia rat models were constructed in the present study. Endogenous metabolites in rat plasma were analyzed using the GC/TOF-MS-based metabonomic method. Significant metabolic differences were observed between the control and two model groups, and the three groups were distinguished clearly by pattern recognition. Compared with those of the control, the levels of hydroxyproline, threonic acid, glutamine and citric acid were strikingly up- or down-regulated in model rats. The metabolites contributing most to the classification between the two "pattern" rats were identified, such as valine, serine, threonine, ornithine, hydroxyproline, lysine, 2-hydroxybutanoic acid, 3-hydroxybutanoic acid, galactofuranose and inositol. These compounds were indicated as the potential biomarkers. The results suggested that the two "patterns" are involved in dysfunction in oxidative stress, energy metabolism and amino acid metabolism. These findings also provided the substantial foundation for exploring the scientific connotation of these two "Zhengxing (pattern types)" of myocardial ischemia, and "Bianzheng (pattern identification)".
本研究构建了心肌缺血大鼠模型的中医“心血瘀阻证”和“气阴两虚证”概念。采用基于气相色谱/飞行时间质谱的代谢组学方法分析大鼠血浆中的内源性代谢物。在对照组与两个模型组之间观察到显著的代谢差异,通过模式识别可将三组清晰区分。与对照组相比,模型大鼠体内羟脯氨酸、苏糖酸、谷氨酰胺和柠檬酸的水平显著上调或下调。确定了对两种“证型”大鼠分类贡献最大的代谢物,如缬氨酸、丝氨酸、苏氨酸、鸟氨酸、羟脯氨酸、赖氨酸、2-羟基丁酸、3-羟基丁酸、呋喃半乳糖和肌醇。这些化合物被表明为潜在生物标志物。结果提示,这两种“证型”涉及氧化应激、能量代谢和氨基酸代谢功能障碍。这些发现也为探索心肌缺血这两种“证型”的科学内涵及 “辨证” 提供了坚实基础。