压力超负荷大鼠心房颤动易感性及基于基因测序的分子机制  

Susceptibility of atrial fibrillation in pressure overload rats and molecular mechanism based on gene sequencing

作　　者：姚青海[1] 尤秉辰 李曦铭[1] 陈炳伟[1] YAO Qing-hai;YOU Bing-chen;LI Xi-ming;CHEN Bing-wei(Department of Cardiology,Tianjin Chest Hospital,Tianjin,300022,China)

机构地区：[1]天津市胸科医院心血管内科,天津300022

出　　处：《中华高血压杂志》2021年第12期1222-1230,共9页Chinese Journal of Hypertension

基　　金：天津市胸科医院院级课题(2018XKZ11);南开大学药物化学生物学重点实验室开放基金课题(2018080)。

摘　　要：目的通过压力超负荷模型,探讨高血压条件下心房颤动易感性变化及分子机制。方法12周龄雄性SD大鼠32只,随机分为对照组(n=15)和腹主动脉缩窄(AAC)组(简称模型组,n=17)。模型组采用7号针头(外径0.7mm)制备AAC模型,对照组不进行AAC,其余步骤相同。比较2组大鼠术后4周心脏超声学、血流动力学指标(每组取5只)和心脏电生理指标(P波离散度、心房间传导时间和左心房传导时间、心房有效不应期,每组取6只)及心房颤动易感性(心房颤动诱发率、持续时间、非自行终止性心房颤动发生率)的变化。提取对照组、模型组动物左心房组织mRNA,利用基因组测序方法筛选差异表达基因,并通过富集分析、蛋白互作网络分析,探索关键的分子靶点。结果超声指标中,模型组左心房直径[(4.08±0.43)比(3.57±0.42)mm,t=2.376,P=0.030]、舒张期和收缩期室间隔厚度[(2.44±0.40)比(2.05±0.24)mm,t=2.167,P=0.046;(3.44±0.42)比(2.98±0.35)mm,t=2.304,P=0.035]高于对照组,左心室射血分数低于对照组[(61.36±8.62)%比(71.70±8.53)%,t=2.406,P=0.029]。模型组左心室收缩压[162.5(159.4~164.2)比132.6(130.8~136.1)mm Hg,Z=-2.611,P=0.009]、主动脉收缩压[157.2(154.7~162.1)比127.1(126.1~129.9)mm Hg,Z=-2.617,P=0.009]、外周动脉收缩压[151.0(149.0~155.0)比124.0(120.0~127.0)mm Hg,Z=-3.134,P=0.002]高于对照组。模型组左心房传导时间、心房间传导时间高于对照组(均P<0.05)。模型组心房颤动持续时间长于对照组[15.00(12.75~18.00)比0(0~2.25)s,Z=-2.945,P=0.003]。模型组在不同频率Burst刺激下,右心房刺激时心房颤动诱发率高于左心房刺激(13/60比3/60,χ^(2)=7.212,P=0.007)。模型组非自行终止性心房颤动发生率高于对照组(10%比0%,Fisher确切概率检验,P<0.001)。2组间P波离散度差异无统计学意义(P>0.05)。对照组、模型组左心房组织基因组测序筛选出5829个差异表达基因。京都基因与基因组百科全书(KEGG)、�Objective To explore the change and molecular mechanism of atrial fibrillation(AF)susceptibility in pressure-overload hypertension rats.Methods Thirty two 12-week-old male SD rats were randomly divided into control group(n=15)and abdominal aorta constriction(AAC)group(model group,n=17).ACC model was established by 0.7mm needles.In control group other steps were the same except ACC.Four weeks after operation,the changes of echocardiological,hemodynamic indexes(5rats in each group),cardiac electrophysiological indexes[P wave dispersion,left atrial condution time(LACT),interatrial conduction time(IACT),effective refractory pe-riod(ERP),6rats in each group]and atrial fibrillation susceptibility(atrial fibrillation rate,duration,onset of nonself-terminating AF)were compared between the 2groups.The mRNA of left atrial samples from control and model groups were extracted,and differently expressed genes(DEG)were selected by genome sequencing,and potential molecular targets were explored by enrichment analysis and protein-protein interaction(PPI)network analysis.Results The left atrial diameter[(4.08±0.43)vs(3.57±0.42)mm,t=2.376,P=0.030],diastolic and systolic inter-ventricular thickness[(2.44±0.40)vs(2.05±0.24)mm,t=2.167,P=0.046;(3.44±0.42)vs(2.98±0.35)mm,t=2.304,P=0.035]in model group were higher,and left ventricular ejection fraction[(61.36±8.62)%vs(71.70±8.53)%,t=2.406,P=0.029]was lower than those of control group.The left ventricular systolic pressure[162.5(159.4-164.2)vs 132.6(130.8-136.1)mm Hg,Z=-2.611,P=0.009],aortic systolic pressure[157.2(154.7-162.1)vs 127.1(126.1-129.9)mm Hg,Z=-2.617,P=0.009]and peripheral arterial systolic blood pressure[151.0(149.0-155.0)vs 124.0(120.0-127.0)mm Hg,Z=-3.134,P=0.002]in model group were higher than those in the control group.The LACT and IACT in model group were also higher than those in the control group(all P<0.05).The duration of AF in the two groups were 15.00(12.75-18.00)and 0(0-2.25)s,which was higher in model group than in control group(Z=-2.945,P=0.003).In the m

关 键 词：心房颤动 高血压 基因测序 线粒体 

分 类 号：R541.75[医药卫生—心血管疾病]