老年复发性房颤病人血浆DNMT3A表达对PI3K/Akt信号通路的影响  

EFFECTS OF SERUM DNMT3A EXPRESSION ON PI3K/AKT SIGNALING PATHWAY IN ELDERLY PATIENTS WITH RECURRENT ATRIAL FIBRILLATION

作　　者：周盼盼 赵映璇 赵玉兰[1] ZHOU Panpan;ZHAO Yingxuan;ZHAO Yulan(Department of Cardiology,the Second Affiliated Hospital of Zhengzhou University,Zhengzhou 450000,China)

机构地区：[1]郑州大学第二附属医院心血管内科,河南郑州450000 [2]河南大学附属颐和医院CCU

出　　处：《青岛大学学报（医学版）》2022年第6期880-884,共5页Journal of Qingdao University(Medical Sciences)

基　　金：河南省医学科技攻关计划项目(LHGJ2019-1724)。

摘　　要：目的 探讨老年复发性心房颤动(房颤)病人血浆DNA甲基转移酶3A(DNMT3A)的表达及其对microRNA-200b(miR-200b)和磷脂酰肌醇3-激酶(PI3K)/蛋白激酶B(Akt)信号通路表达的影响,为房颤的分子靶向治疗提供参考。方法 选择2020年1月—2021年6月在我院诊断为非瓣膜性房颤的老年病人184例,包括初发房颤102例(初发组)和复发房颤82例(复发组),另选择80例性别和年龄匹配的健康老年人作为对照组。采用彩色多普勒超声检测左心房和左心室体积以及左心室射血分数(LVEF),放射免疫法检测血清N末端脑钠肽前体(NT-proBNP)水平,实时定量PCR(qRT-PCR)检测血清DNMT3A mRNA和miR-200b表达,Western blot法检测PI3K和Akt蛋白表达。结果 复发组左心房体积比初发组和对照组增大,差异具有统计学意义(F=8.635,P<0.05),但左心室体积、LVEF和血清NT-proBNP水平差异无显著性(P>0.05)。复发组血清DNMT3A mRNA和PI3K、Akt蛋白水平比初发组和对照组显著升高,而miR-200b水平显著降低,差异具有统计学意义(F=46.498~219.094,P<0.05)。Pearson检验结果显示,血清DNMT3A mRNA水平与左心房容积和容积指数呈正相关(r=0.829、0.810,P<0.05),PI3K和Akt蛋白表达与左心房容积和容积指数呈正相关(r=0.653~0.868,P<0.05),miR-200b与左心房容积和容积指数、血清DNMT3A mRNA水平、PI3K和Akt蛋白表达均呈负相关(r=-0.964~-0.777,P<0.05)。结论 DNMT3A可能通过降低miR-200b表达和提高PI3K/Akt信号通路活性参与老年复发性房颤的发生。Objective To investigate the serum expression of DNA methyltransferase 3a(DNMT3A) in elderly patients with recurrent atrial fibrillation and its effects on the expression of microRNA-200b(miR-200b) and the phosphatidylinositol 3-kinase(PI3K)/protein kinase B(Akt) signaling pathway, and to provide a reference for molecular targeted therapy of atrial fibrillation. Methods We selected 184 elderly patients who were diagnosed with nonvalvular atrial fibrillation at our hospital from Jan-uary 2020 to June 2021, including 102 patients with new-onset atrial fibrillation(new-onset group) and 82 patients with recurrent atrial fibrillation(recurrent group), with 80 age-/sex-matched healthy elderly people as control group. Color Doppler ultrasonography was performed to measure left atrial volume, left ventricular volume, and left ventricular ejection fraction(LVEF). Serum N-terminal prohormone of brain natriuretic peptide(NT-proBNP) levels were determined by radioimmunoassay. Serum DNMT3A mRNA and miR-200b expression was determined by quantitative real-time PCR. PI3K and Akt protein expression was measured by Western blot. Results The recurrent group had a significantly larger left atrial volume than the new-onset and control groups(F=8.635,P<0.05). There were no significant differences in left ventricular volume, LVEF, and serum NT-proBNP levels(P >0.05). Compared with those in the new-onset and control groups, serum DNMT3A mRNA and PI3K/Akt protein levels were significantly higher, while miR-200b levels were significantly lower(F=46.498-219.094,P<0.05). Pearson analysis revealed that serum DNMT3A mRNA levels were positively correlated with left atrial volume and volume index(r=0.829,0.81;P<0.05);PI3K/Akt protein expression was positively correlated with left atrial volume and volume index(r=0.653-0.868,P<0.05);and miR-200b expression was negatively correlated with left atrial vo-lume and volume index as well as serum expression of DNMT3A mRNA and PI3K/Akt protein(r=-0.964 to-0.777,P<0.05). Conclusion DNMT3A may participate

关 键 词：心房颤动 老年人 复发 DNA修饰甲基酶类 PI3K/AKT信号通路 微RNAS 

分 类 号：R541.75[医药卫生—心血管疾病]