慢性间歇低氧对SD大鼠心房电重构的影响  

Effects of chronic intermittent hypoxia on atrial electrical remodeling in rats

作　　者：张凯 马敬霞[3] 马作旺[4] 杨禹 李广平 ZHANG Kai;MA Jing-xia;MA Zuo-wang;YANG Yu;LI Guang-ping(Department of Cardiology,Beijing Shijitan Hospital,Beijing 100038;Tianjin Key Laboratory of Ionic-Molecular Function of Cardiovascular disease,Department of Cardiology,Tianjin Institute of Cardiology,Second Hospital of Tianjin Medical University,Tianjin 300211;Department of Neurology,Affiliated Hospital of Binzhou Medical College,Binzhou 256603;Department of Cardiology,Tianjin Chest Hospital,Tianjin Cardiovasular Institute,Tianjin 300222,China)

机构地区：[1]首都医科大学附属北京世纪坛医院心血管内科,北京100038 [2]天津医科大学第二医院心脏科、天津心血管病离子与分子机能重点实验室、天津心脏病学研究所,天津300211 [3]滨州医学院附属医院神经内科,滨洲256603 [4]天津市胸科医院心内科,天津市心血管病研究所,天津300222

出　　处：《中国应用生理学杂志》2022年第5期385-391,共7页Chinese Journal of Applied Physiology

基　　金：国家自然科学基金(81570304);天津市卫生健康科技项目(TJWJ2022QN071)。

摘　　要：目的:探究慢性间歇低氧(CIH)对SD大鼠心房电重构的影响,阐释CIH促进心房颤动(AF)发生发展的可能机制。方法:80只雄性SD大鼠随机分为对照组(Control)、慢性间歇低氧组/模型组(CIH)每组各40只。模型组大鼠每日接受间歇低氧8 h,持续30 d。行超声心动图、血流动力学检查之后,进行体外心脏电生理学实验、病理学实验及分子生物学实验。电生理实验检测心房AF易感性,Masson染色观察心房肌组织纤维化程度,Western blot检测心房组织中Na _(v) 1.5、Ca_(v) 1.2及K_(v) 4.3的蛋白表达水平。全细胞膜片钳实验中,电流钳模式下记录心房肌细胞动作电位(AP),并计算比较动作电位时程(APD)。电压钳模式下记录比较I_(Na)、I_(Ca)-L、I_(to)电流密度及通道动力学参数。结果:与对照组相比,模型组大鼠心房纤维化程度增加(P<0.01)、AF易感性升高(P<0.05),Na _(v) 1.5、Ca_(v) 1.2(P<0.05)、K_(v) 4.3(P<0.05)的表达水平降低,心房肌细胞的APD_(90)及APD_(50)延长,I_(Na)、I_(Ca-L)(P<0.01)、I_(to)(P<0.01)电流密度降低。结论:CIH导致离子通道亚基表达水平、离子流强度及APD的改变,进而AF诱发率升高,这些变化可能是其促进AF发生发展的机制。Objective:The aim of this study was to investigate the effects of chronic intermittent hypoxia(CIH)on atrial electrical remodeling in Sprague-Dawley(SD)rats,which provide the explication for the mechanisms of CIH promoting atrial fibrillation(AF).Methods:Eighty SD rats were randomly divided into 2 groups:control group and CIH group(n=40).CIH rats were subjected to CIH 8 h/d for 30 days.After the echocardiography and hemodynamics examination,cardiac electrophysiological experiments,histological experiments,and molecular biological experiments were executed.AF susceptibility was measured by isolated heart electrophysiological experiments.Masson's trichrome stain was used to assess the degree of atrial fibrosis.The protein expression levels of sodium voltage-gated channel alpha subunit 5(SCN5A/Na _(v) 1.5),calcium voltage-gated channel subunit alpha1 C(CACNA1C/Ca_(v) 1.2)and potassium voltage-gated channel subfamily D member 3(KCND3/K_(v) 4.3)were measured by Western blot.In whole-cell patch clamp experiments,current clamp mode was used to record AP,and APD_(90) and APD_(50) were analyzed and compared between the two groups.In voltage clamp mode,I_(Na),I_(Ca)-L,I_(to) and their kinetic parameters were recorded and compared between the two groups.Results:Compared to the control rats,atrial interstitial collagen deposition(P<0.01)and AF inducibility(P<0.05)were increased in CIH rats,whereas the expression levels of Na _(v) 1.5,Ca_(v) 1.2 and K_(v) 4.3 were decreased(P<0.05).APD_(90) and APD_(50) in CIH rats’atrial myocytes were longer than those of control rats,and CIH rats showed decreased current density of I_(Na),I_(Ca-L)(P<0.01)and I_(to)(P<0.01).Conclusion:CIH-induced changes in the protein expression levels of ion channel subunits,current intensity,APD,and AF susceptibility,which may be the mechanisms of CIH promoting AF.

关 键 词：心房颤动 慢性间歇低氧 心房重构 离子通道 大鼠 

分 类 号：R541.7[医药卫生—心血管疾病]