药学学报, 2022, 57(5): 1452-1458
引用本文:
王冠杰, 郑海涛, 杜镇, 杨文杰, 王玥琛, 蒋海强, 田振华. 基于1H NMR代谢组学及分子对接技术的异钩藤碱调控自发性高血压大鼠海马代谢研究[J]. 药学学报, 2022, 57(5): 1452-1458.
WANG Guan-jie, ZHENG Hai-tao, DU Zhen, YANG Wen-jie, WANG Yue-chen, JIANG Hai-qiang, TIAN Zhen-hua. Effects of isorhyncophylline on hippocampal metabolism using 1H NMR-based metabolomics combined with molecular docking analysis[J]. Acta Pharmaceutica Sinica, 2022, 57(5): 1452-1458.

基于1H NMR代谢组学及分子对接技术的异钩藤碱调控自发性高血压大鼠海马代谢研究
王冠杰1, 郑海涛2, 杜镇1, 杨文杰1, 王玥琛1, 蒋海强3,4,5, 田振华3,4,5*
1. 山东中医药大学药学院, 山东 济南 250355;
2. 平度市人民医院, 山东 青岛 266700;
3. 山东中医药大学实验中心, 山东 济南 250355;
4. 山东省中医药基础研究重点实验室, 山东 济南 250355;
5. 山东中医药大学教育部中医药经典理论重点实验室, 山东 济南 250355
摘要:
本实验旨在采用核磁共振代谢组学和分子对接方法,分析异钩藤碱对自发性高血压大鼠海马组织内源性代谢物的调控作用。将12只自发性高血压大鼠随机分为模型组和给药组,每组6只,6只WKY大鼠作为对照组。给药组每日给予0.3 mg·kg-1的异钩藤碱治疗,对照组和模型组每日均给予等量生理盐水。动物实验经过山东中医药大学实验动物伦理委员会批准(编号:SDUTCM20210721002)。连续给药8周后取各组大鼠海马组织,采用1H NMR方法结合模式识别技术检测分析3组大鼠海马组织,寻找差异性代谢产物并分析相关代谢通路,通过京都基因与基因组百科全书数据库查找差异代谢物的代谢靶点,将异钩藤碱与核心靶点使用分子对接技术进行对接验证。主成分分析及偏最小二乘判别分析结果显示,各组分类趋势明显。共筛选出7个差异性代谢物,这些代谢物主要涉及到糖代谢和谷氨酸代谢。分子对接技术表明异钩藤碱与9个相关蛋白靶点结合较好。上述研究结果提示,异钩藤碱调控自发性高血压大鼠海马组织的能量代谢和谷氨酸代谢异常。
关键词:    高血压      代谢组学      分子对接      异钩藤碱      海马     
Effects of isorhyncophylline on hippocampal metabolism using 1H NMR-based metabolomics combined with molecular docking analysis
WANG Guan-jie1, ZHENG Hai-tao2, DU Zhen1, YANG Wen-jie1, WANG Yue-chen1, JIANG Hai-qiang3,4,5, TIAN Zhen-hua3,4,5*
1. School of Pharmaceutical Sciences, Shandong University of Traditional Chinese Medicine, Jinan 250355, China;
2. Pingdu People's Hospital, Qingdao 266700, China;
3. Experimental Center, Shandong University of Traditional Chinese Medicine, Jinan 250355, China;
4. Shandong Provincial Key Laboratory of Traditional Chinese Medicine for Basic Research, Jinan 250355, China;
5. Key Laboratory of Traditional Chinese Medicine Classical Theory, Ministry of Education, Shandong University of Traditional Chinese Medicine, Jinan 250355, China
Abstract:
The purpose of this study was to investigate the effect of isorhyncophylline on hippocampal endogenous metabolites in spontaneously hypertensive rats (SHR) by 1H NMR metabolomics and molecular docking. Twelve SHR were randomly divided into a model group and a treatment group. Six Wistar-Kyoto rats were selected as a control group. The rats in the treatment group were administered isorhyncophylline (0.3 mg·kg-1) while the rats in the other two groups were treated with the same amount of sterilized saline solution. Animal experiment was authorized by the Ethics Committee of Shandong University of Traditional Chinese Medicine (No. SDUTCM20210721002). Hippocampal tissues were removed after administration for 8 weeks and assayed by 1H NMR based metabolomics technology combined with a pattern recognition method to find characteristic metabolites, and the metabolic targets were retrieved from the Kyoto Encyclopedia of Genes and Genomes database. Molecular docking technology was used to evaluate binding of isorhyncophylline to the core targets. The results of a principal components analysis (PCA) and partial least squares discriminant analysis (PLS-DA) showed a clear cluster of samples among three groups. There were seven differentially altered metabolites, and glucose metabolism and glutamate metabolism were the principal related pathways. Molecular docking indicated that isorhyncophylline had good binding properties with nine key candidate target proteins. According to the above research results, isorhyncophylline can influence energy metabolism and glutamate metabolism in the hippocampus.
Key words:    hypertension    metabolomics    molecular docking    isorhyncophylline    hippocampus   
收稿日期: 2021-11-01
DOI: 10.16438/j.0513-4870.2021-1568
基金项目: 国家自然科学基金资助项目(81774173);2019年山东省高等学校“青创科技计划”立项(2019KJM005);2018年山东省自然科学基金重大基础研究项目(ZR2018ZC1157).
通讯作者: 田振华,Tel:86-531-89628014,E-mail:tianzhenhuatina@163.com
Email: tianzhenhuatina@163.com
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