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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

Hypoglycemic Mechanism of Ziya Biti Tablet Based on LC-MS Metabolomics Technique
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摘要 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。 Objective: To observe the hypoglycemic effect of Uygur medicine Ziya Biti tablet on the type2 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 lip
作者 张彩娟 晋小雁 邱敏懿 张驰 罗凌龙 王敏 赵保胜 王学勇 ZHANG Cai-juan;JIN Xiao-yan;QIU Min-yi;ZHANG Chi;LUO Ling-long;WANG Min;ZHAO Bao-sheng;WANG Xue-yong(School of Chinese Materia Medica,Beijing University of Chinese Medicine,Beijing 102488,China;Beijing Institute of Chinese Medicine,Beijing University of Chinese Medicine,Beijing 100029,China)
出处 《中国实验方剂学杂志》 CAS CSCD 北大核心 2019年第8期141-147,共7页 China Journal of Experimental Traditional Medical Formulae
基金 国家自然科学基金项目(81773841) 中央本级重大增减支项目(2060302).
关键词 孜亚比提片 2型糖尿病(T2DM) 糖尿病 液相色谱-质谱(LC-MS) Ziya Biti tablet type 2 diabetic(T2DM) diabetes LC-MS
作者简介 第一作者:张彩娟,在读硕士,从事民族药药效及代谢组学研究,E-mail:18513031449@126.com;通讯作者:王学勇,博士,教授,博士生导师,从事药用植物与分子生药学,民族药新药研发工作,Tel:010-64287660,E-mail:wxyph.d@163.com。
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