代谢组学策略评价银杏提取物对高脂诱导动脉粥样硬化金黄地鼠代谢紊乱的药效作用(英文)  

Metabonomic Approach to Evaluating Pharmacodynamics of Ginkgo biloba Extract on the Perturbed Metabolism in Hamsters with Atherosclerosis by High Fat Diet

作　　者：查伟斌[1] 阿基业[1] 王广基[1] 朱萱萱[2] 顾胜华[1] 曹蓓[1] 严蓓[1] ZHA S.Beth 郝海平[1] 黄青[1] 刘林生[1] 石建[1] 孙建国[1] 

机构地区：[1]中国药科大学药物代谢动力学重点实验室,南京210009 [2]江苏省中医院动物药理实验室,南京210029 [3]Department of Microbiology&Immunology,Virginia Common wealth University

出　　处：《中国天然药物》2011年第3期232-240,共9页

基　　金：supported by the National Nature Science Foundation of China (No.30630076);the National New Drug Creation Special Programme Grants (Nos.2009ZX09304-001,20092X09502-004,and 2009ZX09313-008)~~

摘　　要：目的:研究银杏提取物对高脂诱导动脉粥样硬化金黄地鼠代谢紊乱的纠正作用。方法:基于气相色谱/飞行时间质谱(GC/TOF-MS)检测技术的代谢组学方法,分析比较高脂诱导0、3、6、12周及银杏提取物质干预的金黄地鼠血清中的内源性小分子代谢物,多元统计分析银杏提取物抗动脉粥样硬化相关代谢谱差异及潜在生物标志物。结果:在高脂诱导下,模型动物血清总胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白胆固醇(LDL-C)、动脉斑块及血清代谢组均有显著变化。银杏提取物给药后不仅显著降低血清中TC和LDL-C,同时也使高脂诱导偏离的血清代谢谱向正常代谢谱靠近。在动脉粥样硬化的血清生物标志物中,银杏提取物给药后,8个代谢物琥珀酸、甘油酸、亚油酸、花生四烯酸、1-单油酰基甘油、β-生育酚、胆甾-5-烯和赖氨酸回归正常;另外6个代谢物酪氨酸、油酸、2-单油酰基甘油、γ-生育酚、α-生育酚和脱氧胆酸趋向正常。结论:研究结果提示银杏提取物抗动脉粥样硬化效果与其对脂质代谢、胆酸合成及氨基酸代谢的调控密切相关。这将为进一步探讨银杏提取物抗动脉粥样硬化的药效作用机制和特点提供研究基础。AIM： To investigate the effects of Ginkgo biloba extract （GBE） on the perturbed metabolism of a diet-induced atherosclerosis hamster model. METHODS： Gas chromatography coupled with time-of-flight mass spectrometry （GC/TOF-MS） spectroscopy was used to profile serum samples of hamsters induced by high fat diet for 0, 3, 6, 12 weeks, and hamsters administered with GBE in the meanwhile. Multivariate analyses were employed to identify treatment-related fingerprint and potential biomarkers regarding the anti-atherosclerosis effect and mechanisms of GBE. RESULTS： For the model animals, high fat diet （HFD） resulted in a gradual elevation of serum cholesterol and triglyceride, low-density lipoprotein cholesterol （LDL-C）, lesion in aorta arch, and a dynamic trajectory of the metabonomic profile. GBE treatment did not only lead to a marked reduction in total cholesterol and LDL-C levels in hamster serum, but also showed regulatory effects on serum metabolome and restored their scores plot close to normal. Amongst the discriminatory metabolites in serum that characterize atherosclerosis, 8 metabolites restored to normal after treatment with GBE, including succinic acid, glyceric acid, linoleic acid, arachidonic acid, 1-monooleoylglycerol, β-tocopherol, cholest-5-ene, lysine, while 6 metabolites were regulated towards normal, including tyrosine, oleic acid, 2-monooleoylglycerol, γ-tocopherol, α-tocopherol and deoxycholic acid. CONCLUSION： These results indicate that the effect of GBE on the metabolites is involved in lipid metabolism, bile acid synthesis and amino acids turn-over, and is indirect in anti-atherosclerosis effect of GBE. GC/MS-based metabonomics is a potential approach to exploring pharmacological mechanism of GBE effects and to the assessment of pharmacodynamics.

关 键 词：代谢组学 抗动脉粥样硬化 GC/MS 多变量分析 银杏提取物 

分 类 号：R965[医药卫生—药理学]