采用氢核磁共振(~1H NMR)代谢组学技术,并结合多元统计分析方法,研究2型糖尿病(T2DM)大鼠血清中内源性代谢物的变化,并比较葛根芩连汤(GQD)饮片与煮散对其干预作用。采用高糖高脂饲料联合链脲佐菌素(STZ)复制T2DM大鼠模型,比较GQD饮片与煮散对大鼠一般情况、体质量及空腹血糖(FBG)的影响。GQD饮片与煮散均能改善T2DM大鼠一般情况、体质量和FBG。主成分分析结果显示,正常对照组、模型组、阳性药组、GQD饮片组和煮散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。与正常对照组比较,模型组大鼠血清中3-羟基丁酸、氧化三甲胺、甘氨酸、β-葡萄糖和α-葡萄糖的含量升高,乳酸、极低密度脂蛋白、醋酸、谷氨酸、蛋氨酸、谷氨酰胺、丙酮酸、肌酸、胆碱和甘油的含量降低。GQD饮片和煮散干预后均能不同程度地回调其中14个标志物。两种剂型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作用,未表现出显著差异。本研究结果从代谢组学的角度为GQD煮散的临床应用提供了实验数据和理论基础。
To investigate the difference of Gegen Qinlian Decoction(GQD) piece and boiled powder in the treatment of type 2 diabetes(T2DM), the characteristic of overall metabolite profile was examined in the serum of T2 DM rats with ~1H NMR-based metabolomics combined with the multivariate statistical analysis. A rat model of T2 DM was established by feeding of high glucose and high fat diet followed by a streptozotocin(STZ) treatment. The general condition, body weight and fasting blood glucose(FBG) of rats were monitored. GQD piece and boiled powder exhibited activities in the improvement of these parameters. The results of the principal component analysis showed that there was a significant difference in the metabolic profile of the normal control group, the model group, the positive group, the herbal decoction group and the boiled powder group. Totally 15 potential biomarkers were identified by OPLS-DA binding univariate analysis. Compared with normal control group, the serum samples of T2 DM showed a higher level of 3-HB, TMAO, glycine, β-glucose and α-glucose accompanied by lower level of lactate, VLDL, acetate, glutamate, methionine, glutamine, pyruvate, creatine, choline and glycerol. The above results also demonstrated that both piece and boiled powder of GQD could restore 14 of these markers. These results suggested that the disrupted metabolic pathways including energy metabolism, lipid metabolism and amino acid metabolism, were restored by GQD piece and boiled powder. The two formula did not show a significant difference. The results of this study provide experimental data and theoretical basis for the equal activities of GQD piece and boiled powder in clinical application.