基于LC-MS的代谢组学技术分析孜亚比提片的降糖作用机制

目的:观察孜亚比提片对2型糖尿病大鼠的降糖效果,并基于代谢组学技术分析其降糖作用机制。方法:根据临床调研结果对不同组分来源的孜亚比提片进行筛选,筛选出最佳组方配比;并以2型糖尿病大鼠为实验对象进行药效学实验研究,正常组和模型组分别给予相同剂量的生理盐水、孜亚比提片组给予300 mg·kg-1孜亚比提片、二甲双胍组给予300 mg·kg-1盐酸二甲双胍片,每组8只,记录给药后实验组的空腹血糖值及体质量变化并进行数据分析;同时利用超高效液相色谱-线性离子阱/静电场轨道阱组合式高分辨质谱联用(UHPLC-LTQ Orbitrap MS)技术对大鼠血清进行代谢组学分析,采用主成分分析(PCA),偏最小二乘判别分析(OPLS-DA)对不同组别大鼠血清代谢物进行分析,鉴定出潜在生物标记物,并分析维吾尔族药孜亚比提片的降糖作用机制。结果:与正常组比较,模型组大鼠的空腹血糖值升高(P 0. 01);与模型组比较,孜亚比提片组大鼠状态整体较好,毛色光滑,其空腹血糖值也有所下降(P 0. 05),表明孜亚比提片对2型糖尿病大鼠有一定的降糖作用;根据LC-MS代谢组学数据结果最终得到8个生物标记物。与模型组相比孜亚比提片组中L-valine,propionylcarnitine含量均降低(P 0. 05),sphingosine-1-phosphate,LPC(16∶1/0∶0),LPC(18∶0/0∶0),LPC(18∶2/0∶0),LPC(20∶1/0∶0),PC(19∶0/0∶0)的含量均升高(P 0. 05)。结论:孜亚比提片能够降低2型糖尿病大鼠血糖值,并能改善2型糖尿病大鼠的一般生理特征,其作用机制可能与改善氨基酸代谢,脂质代谢有关。

Hypoglycemic Mechanism of Ziya Biti Tablet Based on LC-MS Metabolomics Technique

Objective: To observe the hypoglycemic effect of Uygur medicine Ziya Biti tablet on the type 2 diabetic rats, and analyze the hypoglycemic mechanism based on metabolomic techniques. Method: According to the results of clinical research about different origins of Ziya Biti tablet, the optimal composition was screened out; type 2 diabetic rats were taken as an experimental object in the pharmacodynamic experiments;the control group and model group were given the same dose of normal saline, Ziya Biti bablet group was given 300 mg·kg^-1, the metformin group was given 300 mg·kg^-1 metformin hydrochloride. The fasting blood and weight changes of the experimental group after the treatment were recorded and compared with normal group; ultra-high performance liquid chromatography-linear ion trap/electrostatic field orbit trap combined-type high resolution mass spectrometry (UHPLC-LTQ/Orbitrap MS) technology was used to conduct the metabolomics analysis on the rat serum, and principal component analysis (PCA), partial least squares discriminant analysis (OPLS-DA) on different groups of rat serum metabolites were performed to identify potential biomarkers. Result:Compared with the model group, the rats in the Uygur medicine Ziya Biti tablet showed a healthy states, and the blood glucose were decreased(P<0.05), which indicated that Uygur medicine Ziya Biti tablet had a certain hypoglycemic effect on type 2 diabetic rats. Eight biomarkers were finally obtained according to the results. Compared with model group, L-valine and propionylcarnitine in the Uygur medicine group were decreased(P<0.05), while sphingosine-1-phosphate, LPC (16:1/0:0), LPC (18:0/0:0), LPC (18:2/0:0), LPC 20:1/0:0), PC (19:0/0:0) were elevated(P<0.05). Conclusion:The experimental results showed that Uygur medicine Ziya Biti tablet can reduce the blood glucose of type 2 diabetic rats and allivate general physiological characteristics. The mechanism of action may be related to the improvement of amino acid metabolism and lipid metabolism.