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基于超高效液相色谱-质谱联用技术对葛根芩连汤治疗链脲佐菌素诱导糖尿病大鼠血浆的代谢组学研究

Metabonomic study on the plasma of streptozotocin-induced diabetic rats treated with Ge Gen Qin Lian Decoction by ultra high performance liquid chromatography-mass spectrometry.

作者信息

Zhang Qiyun, Xu Guoliang, Li Jia, Guo Xiaofeng, Wang Hong, Li Bingtao, Tu Jun, Zhang Huashan

机构信息

Key Laboratory of Analytical Chemistry for Biology and Medicine (Ministry of Education), Department of Chemistry, Wuhan University, Wuhan 430072, People's Republic of China; Research Center for Differentiation and Development of Basic Theory of TCM, University of Jiangxi TCM, Nanchang, Jiangxi 330006, People's Republic of China.

Research Center for Differentiation and Development of Basic Theory of TCM, University of Jiangxi TCM, Nanchang, Jiangxi 330006, People's Republic of China.

出版信息

J Pharm Biomed Anal. 2016 Feb 20;120:175-80. doi: 10.1016/j.jpba.2015.12.031. Epub 2015 Dec 22.

Abstract

Changes in endogenous metabolites in the plasma of streptozotocin (STZ)-induced diabetic rats treated with Ge Gen Qin Lian Decoction (GGQLD) were studied. The endogenous compounds in plasma were detected using ultra high performance liquid chromatography coupled with quadrupole-time-of-flight tandem mass spectrometry (UHPLC-Q-TOF-MS). Rats were divided into three groups: control, model, and administration (4.95g crude drug/kg body weight). After the final administration, plasma samples from the three groups were analyzed using metabonomics. The three sample groups could be clearly distinguished. The administration group exhibited a distinct return to the levels of phytosphingosine and dihydrosphingosine of the control group according to the principal component analysis score, and the corresponding biomarkers were defined. Significant changes in endogenous metabolites, such as dihydrosphingosine, phytosphingosine, cholylglycine, and pantothenic acid, were identified in STZ-induced diabetic rats. These biochemical changes are associated with the metabolism of sphingolipids, fats, and acetyl coenzyme-A, which could be useful to further investigate the characteristics of STZ-induced diabetes mellitus and the therapeutic mechanism of action of GGQLD. This metabonomic analysis could provide a useful starting point toelucidate the therapeutic effects and mechanism of action of GGQLD in diabetes mellitus.

摘要

研究了用葛根芩连汤(GGQLD)治疗链脲佐菌素(STZ)诱导的糖尿病大鼠血浆中内源性代谢物的变化。采用超高效液相色谱-四极杆-飞行时间串联质谱(UHPLC-Q-TOF-MS)检测血浆中的内源性化合物。将大鼠分为三组:对照组、模型组和给药组(4.95g生药/kg体重)。末次给药后,采用代谢组学方法对三组大鼠的血浆样本进行分析。三个样本组能够清晰区分。根据主成分分析得分,给药组的植物鞘氨醇和二氢鞘氨醇水平明显恢复到对照组水平,并确定了相应的生物标志物。在STZ诱导的糖尿病大鼠中,鉴定出内源性代谢物如二氢鞘氨醇、植物鞘氨醇、胆酰甘氨酸和泛酸有显著变化。这些生化变化与鞘脂、脂肪和乙酰辅酶A的代谢有关,这可能有助于进一步研究STZ诱导的糖尿病的特征和GGQLD的治疗作用机制。这种代谢组学分析可为阐明GGQLD在糖尿病中的治疗作用和作用机制提供一个有用的起点。

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