药学学报, 2021, 56(4): 1127-1136
引用本文:
张帆, 胡勋秀, 李丁香, 张染, 赵琳琳, 杜岩, 汤道权. 非靶向血液代谢组学研究糖尿病大鼠发生发展及银杏叶提取物干预的作用机制[J]. 药学学报, 2021, 56(4): 1127-1136.
ZHANG Fan, HU Xun-xiu, LI Ding-xiang, ZHANG Ran, ZHAO Lin-lin, DU Yan, TANG Dao-quan. Ginkgo biloba extract ameliorates streptozotocin-induced diabetes in rats as measured by non-targeted metabolomics[J]. Acta Pharmaceutica Sinica, 2021, 56(4): 1127-1136.

非靶向血液代谢组学研究糖尿病大鼠发生发展及银杏叶提取物干预的作用机制
张帆1, 胡勋秀1, 李丁香1, 张染1, 赵琳琳1, 杜岩1, 汤道权1,2*
1. 徐州医科大学, 江苏省新药研究与临床药学重点实验室, 江苏 徐州 221004;
2. 徐州医科大学药物分析教研室, 江苏 徐州 221004
摘要:
基于LC-MS代谢组学的方法,研究糖尿病大鼠发生发展及银杏叶提取物干预的作用机制。采用腹腔注射链脲霉素诱导糖尿病大鼠模型,分正常对照组(NC)、正常银杏叶提取物处理组(N-GBE)、糖尿病模型组(DM)、糖尿病模型银杏叶提取物处理组(D-GBE)。各组大鼠持续干预9周,收集第6~9周各组大鼠血浆进行LC-MS检测,动物实验获得徐州医科大学伦理委员会的批准。结果显示,在第6~9周DM组大鼠血浆中共12个代谢产物发生持续性变化,提示脂肪酸、氨基酸、磷脂、胆汁酸、三羧酸循环、嘌呤等6条代谢通路的异常与DM的发生发展密切相关;GBE可显著调节其中的5个代谢产物,提示GBE可能是通过改善脂肪酸、氨基酸、磷脂、三羧酸循环等代谢通路异常而发挥其延缓DM发生发展的作用。
关键词:    糖尿病      非靶向代谢组学      血浆      银杏叶提取物      LC-MS     
Ginkgo biloba extract ameliorates streptozotocin-induced diabetes in rats as measured by non-targeted metabolomics
ZHANG Fan1, HU Xun-xiu1, LI Ding-xiang1, ZHANG Ran1, ZHAO Lin-lin1, DU Yan1, TANG Dao-quan1,2*
1. Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, Xuzhou 221004, China;
2. Department of Pharmaceutical Analysis, Xuzhou Medical University, Xuzhou 221004, China
Abstract:
Metabolomics based on liquid chromatography coupled with mass spectrometry (LC-MS) was used to study the initiation and development of diabetes in rats, and the ability of Ginkgo biloba extract (GBE) to ameliorate this pathology. Diabetes mellitus (DM) was induced by intra-peritoneal injection of streptozotocin. The rats were randomly divided into a normal control group treated with drug-free solution (NC), a normal control group treated with GBE (N-GBE), a DM group treated with drug-free solution (DM), and a DM group treated with GBE (D-GBE); rats were maintained on this protocol for 9 weeks. Rat plasma was collected from the sixth week to the ninth week and then analyzed with LC-MS. Animal experimentation was approved by the Committee on the Ethics of Animal Experiments of Xuzhou Medical University. Twelve plasma metabolites with continuous differentiation were monitored to indicate dysfunction of metabolic pathways including fatty acid metabolism, phospholipid metabolism, amino acid metabolism, tricarboxylic acid cycle activity, bile acid metabolism, and purine metabolism to confirm the occurrence and development of DM. Treatment with GBE partially reversed the changes seen in five metabolites in DM rats, indicating that GBE could prevent the occurrence and development of DM by acting on fatty acid metabolism, phospholipid metabolism, amino acid metabolism, and the tricarboxylic acid cycle.
Key words:    diabetes mellitus    metabolomics    plasma    Ginkgo biloba leaves extract    LC-MS   
收稿日期: 2021-01-14
DOI: 10.16438/j.0513-4870.2021-0064
基金项目: 江苏省高校自然科学基金重大项目资助(16KJA350001).
通讯作者: 汤道权,E-mail:tangdq@xzhmu.edu.cn
Email: tangdq@xzhmu.edu.cn
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