miR-1调控靶基因HCN4在风湿性心脏病心房颤动中的作用  

Mechanism of miR-1regulation target genes HCN4 in atrial fibrillationof rheumatic heart diseasepatients

作　　者：付勇 毛亮 李妙龄 于风旭 李新 廖斌 邓明彬 FU Yong;MAO Liang;LI Miaoling;YU Fengxu;LI Xin;LIAO Bin;DENG Mingbin(Department of Thoracic and Cardiovascular Surgery,the Affiliated Hospital of Southwest Medical University,Luzhou 646000,China)

机构地区：[1]西南医科大学附属医院心脏大血管外科,四川泸洲646000 [2]西南医科大学心血管医学研究所,四川泸洲646000

出　　处：《实用医学杂志》2019年第15期2419-2423,共5页The Journal of Practical Medicine

基　　金：四川省教育厅基金资助项目（编号：16ZB0200）;四川省卫生计生委资助项目（编号：16PJ553）;西南医科大学附属医院基金资助项目（编号：14027）

摘　　要：目的通过检测风湿性心脏病(风心病)心房颤动(房颤)患者右心耳组织miR-1及其靶基因HCN4表达,探讨miR-1参与风心病房颤的可能机制。方法 36例风心病患者根据是否存在房颤,分为房颤组(AF组)和窦性心律组(SR组),术前均进行心脏彩超、心电图检测,术中取右心耳组织,应用荧光定量PCR技术检测miR-1及靶基因HCN4的表达,免疫组化、Western Blot方法检测HCN4蛋白表达,应用膜片钳技术检测右心耳心肌细胞起搏电流(If)。结果 AF组miR-1基因表达小于SR组[(0.005 0±0.000 7)vs.(0.009 4±0.002 5),P <0.05];而HCN4基因表达水平AF组高于SR组[(0.255 2±0.019 4)vs.(0.159 2±0.013 1),P <0.05];免疫组化AF组HCN4蛋白表达较窦性心律组增强;Western Blot检测HCN4蛋白表达水平AF组高于SR组[(1.170 2±0.055 98)vs.(0.360 6±0.017 78),P <0.05];右心耳心肌细胞起搏电流改变,AF组半稳态激活电压(V1/2)为(-88±5.9)mV,稳态激活曲线斜率(K)为(8.2±1.8);SR组V1/2为(-97±4.5)mV,K为(11.4±2.6)。结论风心病房颤患者miR-1表达降低,调控HCN4基因、蛋白表达增高,导致房颤心肌细胞起搏电流的改变,可能参与风心病房颤的发生。Objective To investigate the possible mechanism of miR-1 involvement in atrial fibrillation(AF)in rheumatic heart disease(RHD)by detecting the expression of miR-1 and its target gene HCN4 in right atrial appendage of RHD patients with AF. Methods Thirty-six RHD patients were divided into AF group and sinus rhythm(SR)groupaccording to the presence or absence of AF. All patients underwent echocardiography and electrocardiogram detection before the operation. Right atrial appendage tissue was taken during the operation. The expression of miR-1 and target gene HCN4 were detected;the expression of HCN4 protein was detected by Immunohistochemistry and Western Blot,and the pacemaker current If of right atrial appendage by patch clamp technique. Results The expression of miR-1 in AF group was lower than that in SR group(0.005 0 ± 0.000 7 vs.0.009 4 ± 0.002 5,P < 0.05). The expression level of HCN4 gene in AF group was higher than that in SR group(0.255 2 ± 0.019 4 vs. 0.159 2 ± 0.013 1,P < 0.05). The expression of HCN4 protein in immunohistochemical AF group was higher than that in SR group. HCN4 protein expression level was higher in AF group than in SR group(1.170 2 ± 0.055 98 vs. 0.360 6 ± 0.017 78,P < 0.05). The right atrial appendage cardiomyocyte pacing current changed:AF group:V1/2(semi-steady-state activation voltage mV):(-88 ± 5.9)mV,K(steady state activation curve slope):(8.2 ± 1.8)and SR group:V1/2(-97 ± 4.5)mV,K(11.4 ± 2.6). Conclusions The expression of miR-1 is decreased in patients with rheumatic atrial fibrillation,but the expression of HCN4 gene and protein is increased,leading to the change of pacemaker current in atrial fibrillation cardiomyocytes,which may be involved in the occurrence of AF in RHD.

关 键 词：心血管病学 风湿性心脏病 窦性心律 心房颤动 MIR-1 超极化激活环核苷酸门控阳离子通道-4 起搏电流 

分 类 号：R541.2[医药卫生—心血管疾病]