基于iTRAQ和质谱技术的合生元对自发性高血压大鼠降压机制蛋白质组学分析  

Proteomics Analysis of Antihypertensive Mechanism of Synbiotics in Spontaneously Hypertensive Rats Based on iTRAQ and Mass Spectrometry

作　　者：陈宇峰[1] 战莹[1] 武晓丹[1] 郭佳[1] 周玉虹 张莉敏[3] 张国旭[1] CHEN Yufeng;ZHAN Ying;WU Xiaodan;GUO Jia;ZHOU Yuhong;ZHANG Limin;ZHANG Guoxu(General Hospital of Shenyang Military Area Command,Shenyang 110016,Liaoning,China;Shenyang Pharmaceutical University,Shenyang 110015,Liaoning,China;Huadong Hospital,Shanghai 200040,China)

机构地区：[1]沈阳军区总医院核医学科,辽宁沈阳110016 [2]沈阳药科大学,辽宁沈阳110015 [3]上海华东医院,上海200040

出　　处：《辽宁中医药大学学报》2018年第10期39-45,共7页Journal of Liaoning University of Traditional Chinese Medicine

基　　金：辽宁省自然科学基金计划重点项目(20170540952)

摘　　要：目的：应用蛋白质组学方法深入地研究含有嗜酸乳杆菌、乳双歧杆菌和低聚木糖的合生元制剂通过调节自发性高血压大鼠肠道菌群实现降血压的机制,为临床治疗高血压提供新的途径,为研究高血压病理生理机制提供新的思路。方法：选取6周龄、雄性7只WKY大鼠和14只SHR大鼠分为对照组、模型组和给药组。给药组每只受试大鼠灌胃给予合生元制剂,7周后分离回肠段,提取并纯化蛋白,采用iTRAQ技术标记肽段,并通过LC-MS/MS分析这些差异表达的蛋白质。用Protein Pilot 4.5软件定性鉴别,并通过STRING进行分析以显示它们的注释和KEGG途径富集。结果：蛋白质组学和免疫组织化学结果显示,6种与PPAR信号途径有关的差异表达蛋白在治疗组回肠中被重新调节,PPARβ和PPARγ显着上调,表明PPARβ和PPARγ信号通路参与合生元降压机制。结论：合生元能通过改变肠道微生物结构,调节PPAR信号通路,激活PPARβ和PPARγ在回肠节段的级联反应,从而改善血压。Objective：On the basis of preliminary experimental results, the mechanism of synbiotics on hypertension by regulating the gut microbiota in spontaneously hypertensive rats（SHR） was further investigated, which also offers a noveltherapy for hypertension and broaches a new insight into the pathophysiological mechanism of hypertension. Methods：Six-week-old male rats were divided into control group（7 WKY rats）, model group（7 SHR rats） and treatment group（7 SHR rats）. Synbiotics were administered intragastrically to treatment group. Ileum segments were isolated 7 weeks later. Proteins were extracted and purified. The peptides were labeled with iTRAQ technology and analyzed for these differentially expressed proteins by LC-MS/MS. Qualitatively identified using Protein Pilot 4.5 software and analyzed by STRING to show enrichment of their annotations and KEGG pathway. Results：The results of proteomics and immunochemistry showed that 6 differential-expression proteins related to PPAR signal pathway could be re-regulated after administration of synbiotics in the ileum and PPAR β and PPARγ were significantly upregulated, indicated that PPAR β and PPARγ signal pathway involved in synbiotic antihypertensive mechanisms. Conclusion：The synbiotics could improve the blood pressure by altering the structure of the intestinal microbiota, regulating the PPAR signal pathway and activating the cascade reactions of PPAR β and PPARγ in the segment of ileum.

关 键 词：合生元 降血压 PPAR途径 蛋白质组学 

分 类 号：R285.5[医药卫生—中药学]