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李淑敏,蒋海强,齐冬梅,杨雯晴.基于代谢组学技术筛选与血压升高相关的差异性代谢物[J].中国比较医学杂志,2022,32(6):23~30.
基于代谢组学技术筛选与血压升高相关的差异性代谢物
Screening of differential metabolites related to elevated blood pressure according to metabolomics technology
投稿时间:2021-11-13  
DOI:10. 3969 / j.issn.1671-7856. 2022. 06. 004
中文关键词:  高血压  代谢组学  相关性分析
英文关键词:hypertension  metabolomics  correlation analysis
基金项目:
作者单位E-mail
李淑敏 山东中医药大学,中医学院, 济南 250355 878954819@ qq. com 
蒋海强 2. 山东中医药大学,中医药创新研究院,济南 250355
4. 山东省中医药基础研究重点实验室,济南 250355
5. 教育部中医药经典理论重点实验室,济南 250355 
 
齐冬梅 3. 山东中医药大学,实验中心, 济南 250355
4. 山东省中医药基础研究重点实验室,济南 250355
5. 教育部中医药经典理论重点实验室,济南 250355 
Dongmei. Qi@ hotmail. com 
杨雯晴 2. 山东中医药大学,中医药创新研究院,济南 250355
5. 教育部中医药经典理论重点实验室,济南 250355 
winnie0416q@ 163. com 
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中文摘要:
       目的 探讨与自发性高血压大鼠(spontaneously hypertensive rats,SHR)血压升高相关的潜在差异性代谢物及代谢通路。 方法 采用非靶向代谢组学技术,研究 5、7、9 周龄的 SHR 与正常组血清代谢物的变化并筛选出不同周龄中共同存在的代谢物,结合 SIMCA-P 软件进行代谢组学数据与血压的相关性分析,发现其对血压升高的影响,利用 MetaboAnalyst 平台对相关代谢物进行通路分析,发现与血压变化相关的通路。 结果 经数据库查询鉴定出 10 个同时存在于不同周龄的差异性代谢物,分别是:胆碱、花生四烯酸、二十二碳六烯酸、血栓烷 B2 、尿酸、 16-羟基十六烷酸、十二烷二酸、胆酸、12(13)-DiHOME、牛磺鹅去氧胆酸。 7 周时血栓烷 B2 与血压正相关,二十二碳六烯酸、尿酸、十二烷二酸、胆酸、花生四烯酸与血压呈负相关;9 周时十二烷二酸、二十二碳六烯酸、胆酸与血压呈正相关,血栓烷 B2 、尿酸、花生四烯酸与血压呈负相关。 花生四烯酸通路是高血压中血压升高的主要影响通路。 结论 以花生四烯酸为主的脂质代谢通路是高血压发生发展的主要影响通路,从整体来看二十二碳六烯酸、胆汁酸发挥一定的降压作用,尿酸促进了血压的升高,而血栓烷 B2 、花生四烯酸在血压升高过程中与血压的相关性尚不统一,但对血压的升高有重要影响。
英文摘要:
       Objective To explore the potential differential metabolites related to blood pressure changes in spontaneously hypertensive rats ( SHR). Methods We applied non-targeted metabolomics technology to study the differences in serum metabolites between SHR and normal groups at 5, 7 and 9 weeks of age, screening out metabolites that co-existed in rats of different ages. We then used SIMCA-P software to analyze the correlation between the metabolomics data and blood pressure and to discover its impact on blood pressure elevation. Finally, we used the MetaboAnalyst platform to conduct a pathway analysis of related metabolites and to identify the related pathways that cause blood pressure changes. Results Through database query, the following 10 differential metabolites that were present at different ages were identified: choline, arachidonic acid, docosahexaenoic acid, thromboxane B2 , uric acid, 16-hydroxyhexadecanoic acid, dodecanedioic acid, cholic acid, 12(13)-DiHOME, and taurochenodeoxycholic acid. At 7 weeks of age, thromboxane B2 was positively correlated with blood pressure, while docosahexaenoic acid, uric acid, dodecanedioic acid, cholic acid, and arachidonic acid were negatively correlated with blood pressure; at 9 weeks, docosahexaenoic acid, dodecanedioic acid and bile acids were positively correlated with blood pressure, while thromboxane B2 , uric acid, and arachidonic acid were negatively correlated with blood pressure. Conclusions The arachidonic acid pathway is the main influencing pathway for the occurrence of hypertension. From overall view, docosahexaenoic acid and bile acids have a certain antihypertensive effect. Uric acid promotes the increase of blood pressure, while the correlation of thromboxane B2 and arachidonic acid with blood pressure is not uniform in the process of blood pressure increase, but they have important effects on the increase of blood pressure.
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