多西环素对慢性间歇低氧导致的大鼠心房电重构的影响

Effects of doxycycline on chronic intermittent hypoxia-induced atrial electrical remodeling in rats

目的探究多西环素(Dox)对慢性间歇性低氧导致的大鼠心房电重构的影响。方法本研究为前瞻性对照研究。90只雄性SD大鼠,14~16周龄,体重240~260 g,按随机数字法分为对照组、模型组和Dox干预组,每组30只。模型组和干预组大鼠接受CIH 8 h/d,共6周。之后采集各组大鼠的基础参数,体外心脏电生理实验检测3组大鼠的心房颤动(房颤)易感性、心房外膜传导速度和传导均质性,通过Western Blot检测比较大鼠心房组织中离子通道亚基的表达水平,全细胞膜片钳实验用于记录和比较心房肌细胞I Na、I_(Ca)-L和I_(to)的电流密度。结果与对照组相比,CIH大鼠的房颤易感性及K_(v)11.1、K ir2.3、K_(Ca)3.1的表达水平显著增加,而I_(Ca)-L、I to和Ca_(v)1.2、K_(v)1.5、K_(v)4.3的表达水平显著降低(P<0.05)。给予Dox干预后显著改善了CIH-D大鼠心房中K_(v)1.5、K_(v)4.3和K_(ir)2.3的表达水平(P<0.05)。结论CIH可导致大鼠心房明显的电重构、结构重构,给予Dox干预后一定程度上改善了这一现象。其干预靶点涉及K_(v)1.5、K_(v)4.3和K_(ir)2.3,表明了Dox在房颤心房重构的潜在作用。

ObjectiveTo investigate the effects of doxycycline(Dox)on chronic intermittent hypoxia(CIH)-induced atrial electrical remodeling in rats.MethodsNinety male SD rats were randomized into 3 groups:Control group,CIH group,and CIH with Dox treatment(CIH-D)group(30 in each group).The rats in CIH and CIH-D rats were subjected to CIH 8 h/d for 6 weeks.Basic parameters of the rats were collected,atrial fibrillation(AF)inducibility,atrial epicardial conduction velocity and conduction inhomogeneity were examined by vitro cardiac electrophysiology experiments.The expression levels of ion channel subunits in atrium were detected by Western Blot.Whole-cell patch clamp experiments were used to recorded I_(Na),I_(Ca)-L,I to.ResultsCompared to the Control group rats,AF inducibility and expression levels of K_(v)11.1,K_(ir)2.3,K_(Ca)3.1 in CIH group rats were significantly increased,while the I Ca-L,I to,and expression levels of Ca_(v)1.2,K_(v)1.5,K_(v)4.3 were decreased.Dox-treatment significantly improved the expression levels of K_(v)1.5,K_(v)4.3 and K ir2.3 in CIH-D group rats.ConclusionCIH caused atrial electrical remodeling in our rats,which was improved by Dox treatment.These changes indicated the potential effects of Dox in AF.