温胆汤治疗高脂血症金黄地鼠的肝脏代谢组学研究

Liver Metabonomics of Wendan Decoction in The Treatment of Hyperlipidemia Golden Hamsters

目的:应用代谢组学方法研究温胆汤对高脂血症金黄地鼠治疗作用的生物学机理。方法:选取34只金黄地鼠随机分为正常组、模型组各11只,温胆汤组12只,采用血脂4项血清生化指标评价高脂血症模型以及温胆汤的干预作用,应用液相色谱-质谱联用(liquid chromatography-mass spectrometry,LC-MS)进行各组大鼠肝组织内源性代谢物分析,采用偏最小二乘法-判别分析(partial least squares discriminant analysis PLS-DA)对多变量数据进行分析。结果:与模型组比较,温胆汤组总胆固醇(total cholesterol,TC)和低密度脂蛋白胆固醇(low density lipoprotein cholesterol,LDL-C)水平明显降低(P<0.05),通过多元数据分析显示模型组与正常组区分明显,温胆汤给药组有明显向正常组回调的趋势,其中甲硫氨酸、磷脂酰胆碱、腺苷、尿刊酸等20余种成分受到了温胆汤的调节。结论:温胆汤可以调节高血脂金黄地鼠的体内异常代谢途径,提示其治疗作用可能通过对磷脂酰胆碱代谢、半胱氨酸和蛋氨酸代谢、嘌呤代谢、谷胱甘肽代谢等生物途径的调节实现。

Objective:To investigate the biological mechanism of Wendan decoction in the treatment of hyperlipidemia golden hamsters by metabonomic method.Methods:Thirty-four golden hamsters were randomly divided into the normal group(n=11),model group(n=11)and Wendan decoction group(n=12).The hyperlipidemia model and the treatment of Wendan decoction were evaluated by measurement of triglycerides(TG),total cholesterol(TC),low-density lipoprotein(LDL)and high-density lipoprotein(HDL).The endogenous metabolites in liver tissue of each group were analyzed by LC-MS,and multivariate data were analyzed by partial least squares discriminant analysis(PLS-DA).Results:Compared with the model group,the levels of TC and LDL-C were decreased(P<0.05).Multivariate data analysis showed that the model group was significantly different from the normal group,and the Wendan decoction group indicated the obvious regulated trend to the normal group.More than 20 components such as methionine,phosphatidylcholine,adenosine and urocanate were regulated by Wendan decoction.Conclusion:Wendan decoction could restore the abnormal metabolic pathway in hyperlipidemia golden hamsters,and it suggested the therapeutic effect may be achieved by regulating phosphatidylcholine metabolism,cysteine and methionine metabolism,purine metabolism,glutathione biosynthesis,and other biological pathways.