三甲胺-N-氧化物调节肾素-血管紧张素系统诱导人脐静脉内皮细胞炎症的作用机制研究  

Study on the mechanism of trimethylamine-N-oxide regulating renin-angiotensin system induced inflammation in human umbilical vein endothelial cells

作　　者：郑平 陈伟 郑艳 ZHENG Ping;CHEN Wei;ZHENG Yan(Department of Vasculocardiology,Fuzhou Traditional Chinese Medicine Hospital,Fujian University of Traditional Chinese Medicine,Fuzhou 350004,China;Department of Critical Care Medicine,Fuzhou Traditional Chinese Medicine Hospital,Fujian University of Traditional Chinese Medicine,Fuzhou 350004,China)

机构地区：[1]福建中医药大学附属福州中医院心血管内科,福建福州350004 [2]福建中医药大学附属福州中医院重症医学科,福建福州350004

出　　处：《中国现代医生》2022年第6期28-32,46,F0003,共7页China Modern Doctor

基　　金：福建省福州市市级科技计划项目(2019-SZ-29)。

摘　　要：目的探讨三甲胺-N-氧化物(TMAO)与肾素-血管紧张素系统(RAS)在人脐静脉内皮细胞(HUVECs)炎症中的关系及作用机制。方法ELISA检测来自2020年9—12月福州市中医院心血管内科的动脉粥样硬化(AS)患者(n=36)与正常人(n=25)血浆中TMAO、血管紧张素Ⅱ(AngⅡ)的表达情况;采用不同梯度的TMAO干预HUVECs细胞诱导炎症;通过CCK-8法检测HUVECs细胞增殖;划痕实验分析HUVECs细胞迁移;血管形成实验分析内皮细胞的功能障碍;通过ELISA实验检测各组HUVECs细胞炎症因子白细胞介素-1β(IL-1β)、白细胞介素-18(IL-18)、内皮型一氧化氮合酶(eNOS)水平;通过WB实验检测RAS系统中血管紧张素原(AGT)、血管紧张素转化酶(ACE)、AngⅡ及血管紧张素受体(ATR)的表达。结果相比于正常人,AS患者血浆中TMAO与AngⅡ高表达,差异有统计学意义(P<0.05);成功建立了不同梯度浓度的TMAO干预HUVECs细胞的炎症模型;TMAO干预后抑制细胞增殖,且呈剂量依赖性;TMAO能够抑制HUVECs细胞的迁移能力;TMAO干预后内皮细胞血管成环数减少,环变小,抑制血管形成;TMAO干预后促进炎症因子IL-1β、IL-18的表达,抑制eNOS的表达;在TMAO干预下RAS系统中的AGT、ACE、ANGⅡ及ATR的表达水平均显著升高。结论TMAO能够调节RAS系统诱导HUVECs炎症。Objective To explore the relationship and mechanism of trimethylamine-N-oxide(TMAO)and renin-angiotensin system(RAS)in the inflammation of human umbilical vein endothelial cells(HUVECs).Methods The expression of the plasma levels of TMAO and AngiotensinⅡ(AngⅡ)in the atherosclerosis(AS)patients(n=36)and the healthy people(n=25)from the Department of Cardiovascular Medicine,Fuzhou Traditional Chinese Medicine Hospital from September to December 2020 were detected by ELISA;different gradients of TMAO was used to interfere with HUVECs to induce inflammation;HUVECs proliferation was detected by CCK-8 method;Scratch test was used to analyze HUVECs migration;the dysfunction of endothelial cells was analyzed by angiogenesis assay;the levels of inflammatory factors,such as interleukin-1β(IL-1β),interleukin-18(IL-18)and endothelial nitric oxide synthase(eNOS),in each group of HUVECs were detected by ELISA;the expression of angiotensinogen(AGT),angiotensin converting enzyme(ACE),AngⅡand angiotensin receptor(ATR)in the RAS system was detected by WB assay.Results Compared with the healthy people,TMAO and AngⅡwere highly expressed in the plasma of AS patients,and there were significant differences(P<0.05);different gradient concentrations of TMAO were successfully established to interfere with the inflammation model of HUVECs;after TMAO intervention,cell proliferation was inhibited in a dose-dependent manner;TMAO was able to inhibit the migration ability of HUVECs;after the intervention of TMAO,the number of endothelial cell vascular loops was decreased and the loops became smaller,which inhibited the formation of blood vessels;after TMAO intervention,the expression of inflammatory factors IL-1βand IL-18 was promoted,and the expression of e NOS was inhibited;under the intervention of TMAO,the expression levels of AGT,ACE,ANGⅡand ATR in the RAS system were significantly increased.Conclusion TMAO can regulate the RAS system to induce the inflammation of HUVECs.

关 键 词：三甲胺-N-氧化物 RAS系统 HUVECs炎症 血管紧张素Ⅱ 

分 类 号：R965[医药卫生—药理学]