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[摘要]
目的 采用氢核磁共振(1H-NMR)代谢组学技术分析2型糖尿病(T2DM)大鼠血清中内源性代谢物的变化,比较葛根芩连汤(GQD)与发酵GQD对其干预作用。方法 采用高糖高脂饲料联合链脲佐菌素(STZ)复制T2DM大鼠模型,分别ig给予GOD与发酵GOD,共给药8周。观察大鼠一般情况并测定其体质量及空腹血糖(FBG);收集大鼠血清样品,对血清1H-NMR图谱进行归属;结合多元统计分析方法,筛选可能的潜在生物标志物。结果 与对照组比较,模型组大鼠体质量减小、FBG升高;GQD与发酵GQD均能改善T2DM大鼠一般情况、体质量和FBG。主成分分析结果显示,对照组、模型组与给药组的代谢轮廓明显区分,并鉴定了15个与T2DM相关的潜在生物标志物。与对照组比较,模型组大鼠血清中3-羟基丁酸、胆碱、甘氨酸、甘油、β-葡萄糖和α-葡萄糖的含量升高,乳酸、极低密度脂蛋白、氧化三甲胺、醋酸、谷氨酸、蛋氨酸、谷氨酰胺、丙酮酸和肌酸的含量降低。GQD和发酵GQD干预后均能不同程度地回调已鉴定的所有标志物。结论 GQD和发酵GQD均可通过调节能量代谢、脂质代谢和氨基酸代谢等途径而发挥治疗T2MD作用,未表现出显著差异,从代谢组学的角度为发酵GQD的临床应用提供了实验数据和理论基础。
[Key word]
[Abstract]
Objective To compare the antidiabetic effects between raw and fermented Gegen Qinlian Decoction (GQD) containing different endogenous metabolites by 1H NMR technology based on metabolomics.Methods The antidiabetic effects were evaluated using high glucose and high fat diet combined with streptozotocin (STZ). The treatment groups were fed with GQD and fermented GQD every day, respectively for 8 weeks.The general condition, body weight and fasting blood glucose (FBG) of rats were observed. The chemical compositions of serum were assigned by 1H NMR spectroscopy. Using the multivariate statistical analysis as the main data analysis methods, potential biomarkers were screened in the model.Results The body weight of the diabetic rats decreased significantly compared to the normal control group after injection of STZ. In addition, the FBG level was significantly increased in the diabetic rats than that in the normal control group. GQD and fermented GQD all can improve the general condition, body mass, and FBG level of T2DM rats. The results of the principal component analysis showed that the metabolic profile of the normal control group, the model group and drug treatment group was significantly differentiated. In total, 15 potential biomarkers associated with T2DM were identified by OPLS-DA binding univariate analysis. The corresponding S-plot combined with VIP > 1 revealed that the major variations in diabetic rats were the elevation of 3-hydroxybutyrate (3-HB), choline, glycine, glycerol, β-glucose, and α-glucose, as well as the decline levels of lactate, very low-density lipoprotein (VLDL), trimethylamine-N-oxide (TMAO), acetate, glutamate, methionine, glutamine, pyruvate, and creatine. Both raw and fermented GQD displayed antidiabetic effects against STZ-induced diabetes by restoring 15 of biomarkers.Conclusion Detailed analysis of the altered metabolite levels indicated that raw and fermented GQD significantly ameliorated the disturbance in glucose metabolism, lipid metabolism, and amino acid metabolism in the therapeutic process of T2DM, while no significant difference was observed between them. The results of this study provide experimental data and theoretical basis for the clinical application of GQD fermentation from the perspective of metabolomics.
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[基金项目]
国家自然科学基金面上项目(81273659)