药学学报, 2020, 55(1): 83-90
引用本文:
郭茜, 李雪嘉, 郭鸿儒, 张娜, 王秀凤, 吴立蓉. 黄芪-山药药对治疗2型糖尿病的尿液代谢组学研究[J]. 药学学报, 2020, 55(1): 83-90.
GUO Qian, LI Xue-jia, GUO Hong-ru, ZHANG Na, WANG Xiu-feng, WU Li-rong. The urinary metabolomics of Astragalus Radix and Dioscoreae Rhizomacomes reveal possible therapeutic mechanisms in the treatment of type 2 diabetes[J]. Acta Pharmaceutica Sinica, 2020, 55(1): 83-90.

黄芪-山药药对治疗2型糖尿病的尿液代谢组学研究
郭茜1,2, 李雪嘉2,3, 郭鸿儒4, 张娜3, 王秀凤5, 吴立蓉1,2
1. 广东药科大学生命科学与生物制药学院, 广东 广州 510006;
2. 广东药科大学广东省生物活性药物研究重点实验室, 广东 广州 510006;
3. 广东药科大学药学院, 广东 广州 510006;
4. 广东药科大学中药学院, 广东 广州 510006;
5. 广东药科大学医学信息工程学院, 广东 广州 510006
摘要:
为了探讨黄芪-山药药对治疗2型糖尿病(T2DM)的作用机制,本研究首次应用氢核磁共振(1H NMR)尿液代谢组学方法研究了黄芪-山药药对对T2DM大鼠的代谢保护机制。将37只SD大鼠随机分为4个组:模型组M,对照组C,黄芪山药组HS,阳性对照组Y(二甲双胍)。利用高脂饲料喂养合并链脲佐菌素(STZ)诱导制备T2DM模型。造模后连续给药8周,随后取其血检测相关生化指标;取其肾脏检测肾脏系数。动物实验获得广东药科大学伦理委员会的批准。通过1H NMR代谢组学方法检测各组大鼠尿液中代谢物的变化,筛选出标志性代谢物。实验结果显示,与对照组比较,模型组大鼠总胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白(L-DLC)、尿素氮(BUN)、糖化血红蛋白(HbA1c)及肾脏系数明显升高,高密度脂蛋白(H-DLC)水平显著降低(P<0.01),在黄芪-山药药对治疗后上述指标均有明显改善。模型组大鼠尿液中共发现20个标志性代谢物,黄芪山药治疗后可不同程度的逆转16个代谢物的变化,其效果与200 mg·kg-1二甲双胍相当。主要涉及丁酸代谢、三羧酸循环(TCA循环)、牛磺酸和亚牛磺酸代谢、酮体的合成与降解、丙酮酸代谢。提示黄芪-山药药对可能主要通过以上5条代谢通路对T2DM起到治疗作用,揭示了黄芪-山药药对对T2DM的治疗机制。
关键词:    山药      黄芪      2型糖尿病      代谢组学      尿液     
The urinary metabolomics of Astragalus Radix and Dioscoreae Rhizomacomes reveal possible therapeutic mechanisms in the treatment of type 2 diabetes
GUO Qian1,2, LI Xue-jia2,3, GUO Hong-ru4, ZHANG Na3, WANG Xiu-feng5, WU Li-rong1,2
1. School of Life Science and Biopharmaceuticals, Guangdong Pharmaceutical University, Guangzhou 510006, China;
2. Key Laboratory of Bioactive Drugs Research in Guangdong Province, Guangdong Pharmaceutical University, Guangzhou 510006, China;
3. School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou 510006, China;
4. School of Traditional Chinese Medicine, Guangdong Pharmaceutical University, Guangzhou 510006, China;
5. College of Medical Information Engineering, Guangdong Pharmaceutical University, Guangzhou 510006, China
Abstract:
1H NMR-based metabonomic analysis was used to elucidate the hypoglycemic mechanism of Astragalus Radix and Dioscoreae Rhizomacomes. Thirty-seven SD rats were divided into four groups:model group (M group), control group (C group), Astragalus Radix and Dioscoreae Rhizomacomes group (HS group), metformin group (Y group). A T2DM model was induced with a high fat diet and streptozotocin (STZ). Drug was continuously administered for 8 weeks, after which blood and the kidneys were collected to determine the biochemical index and the kidney coefficients of each group. Using 1H NMR metabolomics technology, we measured the metabolites in the urine of rats in each group to identify appropriate biomarkers. The results showed that total cholesterol (TC), triglyceride (TG), low density lipoprotein cholesterol (L-DLC), blood urea nitrogen (BUN), hemoglobin A1c (HbA1c) and the kidney coefficients were significantly increased with high density lipoprotein (H-DLC) significantly decreased in the diabetic group, but these changes were largely reversed with treatment with Astragalus Radix and Dioscoreae Rhizomacomes. A total of 20 biomarkers were found in rat urine in the diabetic group and Astragalus Radix and Dioscoreae could reverse the changes of 16 of these metabolites to varying degrees, similar to that of metformin (200 mg·kg-1). The changes in metabolomics mainly involved butanoate metabolism, the tricarboxylic acid (TCA) cycle, taurine and hypotaurine metabolism, synthesis and degradation of ketone bodies, and pyruvate metabolism. Dioscoreae Rhizomacomes and Astragalus Radix may have a therapeutic role in the treatment of diabetes through the above five metabolic pathways, revealing the possible therapeutic mechanisms for Dioscoreae Rhizomacomes and Astragalus Radix.
Key words:    Dioscoreae Rhizomacomes    Astragalus Radix    type 2 diabetes    metabolomics    urine   
收稿日期: 2019-06-06
DOI: 10.16438/j.0513-4870.2019-0453
基金项目: 国家自然科学基金资助项目(81703977).
通讯作者: 吴立蓉,Tel/Fax:86-20-39352552,E-mail:30872950@qq.com
Email: 30872950@qq.com
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