唐春仕,谭利辉,卢新林,陈文江
TANG Chunshi,TAN Lihui,LU Xinlin,CHEN Wenjiang

• 1:郴州市第四人民医院心血管内科
• 2:郴州市第四人民医院急诊科
• 3:广东医科大学附属医院心血管内科

摘要(Abstract)：

目的:探讨血浆中miRNA-296-5p与原发性高血压(EH)的相关性。方法:选取EH患者80例和非EH患者80例,收集两组患者基本病史、心血管疾病用药情况等一般资料,采用qRT-PCR检测其血浆中循环miRNA-296-5p的表达水平,生物信息学预测miRNA-296-5p的靶基因以及其调控的信号通路,ELISA检测两组患者血浆中TGF-β1和ACE2的表达,并分析两者与miRNA-296-5p的相关性。结果:EH组与非EH组在年龄、性别、BMI、基本病史和部分血液学生化指标比较,差异无统计学意义(P>0.05);EH组血浆中循环miRNA-296-5p表达水平明显高于非EH(P<0.01);ROC曲线分析发现曲缺中miRNA-296-5p曲线下面积为0.844 5,95%可信区间为(CI)0.782 5~0.906 4(P<0.01),灵敏度80.00%,特异性90.00%;生物信息学预测发现miRNA-296-5p的靶基因可能为血管转化生长因子-β1(TGF-β1)和血管紧张素转化酶2(ACE2),可能调控血管转化生长因子/SMAD(TGF-β/SMAD)、磷脂酰肌醇-3激酶(PI3K-Akt)、胰岛素/胰岛素生长因子信号通路(Insulin/IGF)、丝裂原活化蛋白激酶(MAPK)和NOTCH等信号通路,并可能参与多种circRNA的调控;ELISA检测发现EH组TGF-β1和ACE2的表达明显高于非EH组(P<0.01),miRNA-296-5与TGF-β1、ACE2均呈正相关(r=0.317 6、0.417 1,P<0.01)。结论:血浆中循环miRNA-296-5p可能通过调控TGF-β1和ACE2导致EH的发生,并可以作为EH新的临床诊断标志物。
Objective:To identify the correlation of plasma miRNA-296-5p with essential hypertension( EH). Methods:80 EH cases and 80 non-EH cases with their general information such as case history and medication on cardiovascular disease,then adopting qRT-PCR to test expression level of circulating miRNA-296-5p,and its biological information was predicted. Then the test carried out ELISA to detect the probable target gene of miRNA-296-5p. Results:There was no statistical difference in age,gender,BMI,basic history and basic laboratory tests between EH group and non-EH group( P > 0. 05); the circulating miRNA-296-5p expression level in EH group was significantly higher than non-EH group( P < 0. 01); ROC curve analysis found that the area under the curve was0. 844 5,and the 95% CI was 0. 782 5-0. 906 4( P < 0. 01); bioinformatics prediction found thatTGF-β1 and ACE2 might be the target gene of miRNA-296-5p,and might regulate TGF-β/SMAD,PI3K-Akt,Insulin/IGF,MAPK and NOTCH signaling pathways together with regulating multiple circRNA.ELISA revealed that TGF-β1 and ACE2 expression levels were significantly higher in EH cases(P<0.01);miRNA-296-5 was positively correlated with TGF-β1 and ACE2(r=0.317 6,0.4 171,P<0.01).Conclusion:Circulating miRNA-296-5p can be a biomarker of EH,and may participate in the mechanism of EH by regulating TGF-β1 and ACE2.

关键词(KeyWords)： 血管转化生长因子β1;血管紧张素转化酶2;高血压;生物标志物;微小RNA-296-5p
transforming growth factor-beta1;angiotensin conrerting enzyme 2;hypertension;biomarkers;circRNA-296-5p

Abstract:

Keywords:

基金项目(Foundation):

作者(Author): 唐春仕,谭利辉,卢新林,陈文江
TANG Chunshi,TAN Lihui,LU Xinlin,CHEN Wenjiang

DOI: 10.19367/j.cnki.1000-2707.2017.03.026

参考文献(References)：

• [1]陈伟伟,高润霖,刘力生,等.《中国心血管病报告2014》概要[J].中国循环杂志,2015(7):617-622.
• [2]Seravalle G,Mancia G,Grassi G.Role of the sympathetic nervous system in hypertension and hypertension-related cardiovascular disease[J].High Blood Press Cardiovasc Prev,2014(2):89-105.
• [3]陈文江,陈灿.微RNA与心房颤动发病机制的研究进展[J].医学综述,2015(5):801-803.
• [4]Philippen LE,Dirkx E,da Costa-Martins PA,et al.Non-coding RNA in control of gene regulatory programs in cardiac development and disease[J].J Mol Cell Cardiol,2015(15)1-5.
• [5]Li M,Zhang J.Circulating microRNAs:potential and emerging biomarkers for diagnosis of cardiovascular and cerebrovascular diseases[J].Biomed Res Int,2015(145):730535.
• [6]廖玉华.MicroRNAs将成为心血管病诊断和治疗的标记物[J].临床心血管病杂志,2015(9):922-923.
• [7]Lu F,Andris HE,Moore XL,et al.Circulating microRNAs as biomarkers for diffse myocardial firosis in patients with hypertrophic cardiomyopathy[J].J Transl Med,2015(13):314.
• [8]孙宁玲,Chen JW,王继光,等.亚洲高血压合并左心室肥厚诊治专家共识[J].中华高血压杂志,2016(07):619-627.
• [9]王继光,吴兆苏,孙宁玲,等.动态血压监测临床应用中国专家共识[J].中华高血压杂志,2015(8):727-730.
• [10]Mendoza-Torres E,Oyarzún A,Mondaca-Ruff D,et al.ACE2 and vasoactive peptides:novel players in cardiovascular/renal remodeling and hypertension[J].Ther Adv Cardiovasc Dis,2015(4):217-37.
• [11]Chu PL,Le TH.Role of collectrin,an ACE2 homologue,in blood pressure homeostasis[J].Curr Hypertens Rep,2014(11):490.
• [12]Meng X,Li X,Zhang P,et al.Circular RNA:an emerging key player in RNA world[J].Brief Bioinform,2016(2):45.

文章评论(Comment)：