基于 GC/MS 的代谢组学分析在研究银杏叶提取物对饮食诱导的高脂血症大鼠的调脂作用中的应用。
Application of GC/MS-based metabonomic profiling in studying the lipid-regulating effects of Ginkgo biloba extract on diet-induced hyperlipidemia in rats.
机构信息
Key Laboratory of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Nanjing, China.
出版信息
Acta Pharmacol Sin. 2009 Dec;30(12):1674-87. doi: 10.1038/aps.2009.173.
AIM
To evaluate the lipid-regulating effects of extract from Ginkgo biloba leaves (EGB) using pharmacological methods and metabonomic profiling in a rat model of diet-induced hyperlipidemia.
METHODS
EGB was orally administered at a dose level of 40 mg/kg in both the EGB-prevention and -treatment groups. All rat samples obtained were examined for known and potential biomarkers and enzyme activity using commercial assay kits and GC/MS-based metabonomic profiling coupled with principal component analysis (PCA).
RESULTS
The data obtained from the assay kits indicated that EGB reduced total cholesterol and low density lipoprotein cholesterol levels and increased high density lipoprotein cholesterol levels in rat plasma obtained from both the EGB-prevention and -treatment groups compared with those of the diet-induced hyperlipidemia group. EGB also increased the activities of lipoprotein lipase and hepatic lipase and excretion of fecal bile acid in rats from the EGB-prevention and-treatment groups. Using GC/MS-based metabonomic analysis, more than 40 endogenous metabolites were identified in rat plasma. PCA of rat plasma samples obtained using GC/MS produced a distinctive separation of the four treatment groups and sampling points within each group. Metabolic changes during hyperlipidemia formation and improvement resulting from EGB treatment were definitively monitored with PCA score plots. Furthermore, elevated levels of sorbitol, tyrosine, glutamine and glucose, and decreased levels of citric acid, galactose, palmitic acid, arachidonic acid, acetic acid, cholesterol, butyrate, creatinine, linoleate, ornithine and proline, were observed in the plasma of rats treated with EGB.
CONCLUSION
EGB exerts multi-directional lipid-lowering effects on the rat metabonome, including limitation of the absorption of cholesterol, inactivation of HMGCoA and favorable regulation of profiles of essential polyunsaturated fatty acid (EFA). Further experiments are warranted to explore the mechanisms of action underlying the lipid-regulating effects of EGB against hyperlipidemia.
目的
采用药理学方法和代谢组学方法评价银杏叶提取物（EGB）在饮食诱导的高脂血症大鼠模型中的调脂作用。
方法
EGB 在预防和治疗组中的剂量水平为 40mg/kg 进行口服给药。使用商业测定试剂盒和基于 GC/MS 的代谢组学分析（与主成分分析 [PCA] 相结合），对大鼠的所有样本进行了已知和潜在生物标志物及酶活性的检测。
结果
从试剂盒获得的数据表明，与饮食诱导的高脂血症组相比，EGB 降低了预防和治疗组大鼠血浆中的总胆固醇和低密度脂蛋白胆固醇水平，增加了高密度脂蛋白胆固醇水平。EGB 还增加了脂蛋白脂肪酶和肝脂肪酶的活性以及预防和治疗组大鼠粪便胆汁酸的排泄。通过基于 GC/MS 的代谢组学分析，鉴定了大鼠血浆中的 40 多种内源性代谢物。使用 GC/MS 对大鼠血浆样本进行 PCA 分析产生了四个治疗组和每个组内采样点的明显分离。通过 PCA 得分图明确监测了高脂血症形成期间的代谢变化和 EGB 治疗的改善。此外，在 EGB 治疗的大鼠血浆中观察到山梨糖醇、酪氨酸、谷氨酰胺和葡萄糖水平升高，柠檬酸、半乳糖、棕榈酸、花生四烯酸、乙酸、胆固醇、丁酸盐、肌酸、亚油酸、鸟氨酸和脯氨酸水平降低。
结论
EGB 对大鼠代谢组产生了多方向的降脂作用，包括限制胆固醇的吸收、抑制 HMGCoA 和对必需多不饱和脂肪酸（EFA）谱的有利调节。需要进一步的实验来探索 EGB 对高脂血症的调脂作用的作用机制。
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