CAJ | 학술논문

目的建立家兔快速心房起搏模型，探讨辛伐他汀对快速心房起搏早期心电图心房有效不应期( AERP )变化及心房L型钙离子通道α1c亚单位蛋白表达的影响。方法42只家兔均分为对照组、心房快速起搏组、辛伐他汀干预组。辛伐他汀干预组每天5 mg/(kg·d)辛伐他汀灌胃2周，其余组以等量生理盐水灌胃2周，对照组不行起搏。心房快速起搏组和辛伐他汀干预组行快速心房起搏(800次/分)建立急性心房纤颤模型，分别测定各组在0、1、2、4、6、8h (记为 P0、P1、P2、P4、P6、P8)时的心房有效不应期(AERP150和AERP200)及AERP200-AERP150的频率适应性，用Western blot法检测急性起搏8 h后右房组织L型钙通道α1c蛋白表达，同时检测各组血脂水平。结果各组动物血脂水平差异无统计学意义。心房快速起搏组在不同基础刺激作用下AERP明显缩短， AERP200-AERP150的频率适应性明显下降(P<0.05)，辛伐他汀干预组AERP缩短程度减轻， AERP200-AERP150频率适应性同对照组相比差异无统计学意义。心房快速起搏组起搏8h后心房肌细胞L型钙通道的α1c亚单位的蛋白表达水平较对照组明显下降( P<0.01)，辛伐他汀干预组蛋白表达水平较对照组下降不明显。结论快速心房起搏早期心房快速起搏组较对照组有效不应期明显缩短、频率适应性降低，辛伐他汀预处理可明显改善不应期缩短程度，快速起搏前后频率适应性基本维持。快速起搏8 h后L型钙通道的α1c亚单位的蛋白表达水平下降，主要的机制可能是与快速起搏引起的钙超载导致离子通道转录水平的下降有关，辛伐他汀预处理可明显减轻蛋白表达水平下降的程度，而不依赖于降血脂效应，可能为辛伐他汀降低心律失常发生率的细胞学离子机制之一。
목적건립가토쾌속심방기박모형，탐토신벌타정대쾌속심방기박조기심전도심방유효불응기( AERP )변화급심방L형개리자통도α1c아단위단백표체적영향。방법42지가토균분위대조조、심방쾌속기박조、신벌타정간예조。신벌타정간예조매천5 mg/(kg·d)신벌타정관위2주，기여조이등량생리염수관위2주，대조조불행기박。심방쾌속기박조화신벌타정간예조행쾌속심방기박(800차/분)건립급성심방섬전모형，분별측정각조재0、1、2、4、6、8h (기위 P0、P1、P2、P4、P6、P8)시적심방유효불응기(AERP150화AERP200)급AERP200-AERP150적빈솔괄응성，용Western blot법검측급성기박8 h후우방조직L형개통도α1c단백표체，동시검측각조혈지수평。결과각조동물혈지수평차이무통계학의의。심방쾌속기박조재불동기출자격작용하AERP명현축단， AERP200-AERP150적빈솔괄응성명현하강(P<0.05)，신벌타정간예조AERP축단정도감경， AERP200-AERP150빈솔괄응성동대조조상비차이무통계학의의。심방쾌속기박조기박8h후심방기세포L형개통도적α1c아단위적단백표체수평교대조조명현하강( P<0.01)，신벌타정간예조단백표체수평교대조조하강불명현。결론쾌속심방기박조기심방쾌속기박조교대조조유효불응기명현축단、빈솔괄응성강저，신벌타정예처리가명현개선불응기축단정도，쾌속기박전후빈솔괄응성기본유지。쾌속기박8 h후L형개통도적α1c아단위적단백표체수평하강，주요적궤제가능시여쾌속기박인기적개초재도치리자통도전록수평적하강유관，신벌타정예처리가명현감경단백표체수평하강적정도，이불의뢰우강혈지효응，가능위신벌타정강저심률실상발생솔적세포학리자궤제지일。
Objective In this research we established rapid atrial pacing rabbit models, to investigate the effects of simvastatin on changes of early atrial effective refractory period (AERP) and protein expression of atrial α1c sub-unit of L-type calcium channel on atrial remodeling. Methods 42 rabbits were randomly divided into 3 groups:control group,rapid pacing group and simvastatin group,simvastatin 5 mg/( kg·d) was given intragastrically daily for two weeks before electrophysiology study in simvastatin group, normal saline was given intragastrically in control and rapid pacing group instead. Control group with no pacing, in simvastatin group and rapid pacing group, right atrium was paced at 800 beats/min for 8 hours to establish acute atrial fibrillation models, right atrial effective re-fractory period(AERP)was measured at the basic cycle length of 200 ms and 150 ms before pacing and 1,2,4,6, and 8 hours after the onset of the pacing, the changes of rate adaptation of AERP (AERP200-AERP150) were ana-lyzed . Right atrium tissue was obtained for measurement of protein expression of atrialα1 c subunit of L-type calcium channel by Western blot. Simultaneously,lipid levels in each group was examined. Results No significant differ-ence in lipid levels among three groups was observed. The AERP was shortened and the rate adaptation of AERP (AERP200-AERP150) disappeared during pacing compared with those before pacing(P<0.05). The shortening of AERP was reversed and AERP200-AERP150 was maintained in simvastatin group. Compared with the control group,the protein expression levels of atrial α1c subunit of L-type calcium channel decreased significantly after 8 hours pacing in rapid pacing group(P<0.01). The protein expression levels of simvastatin group decreased insig-nificantly . Conclusion Atrial rapid pacing can induce the shortening of the AERP and the losing of adaptability to the frequency of AERP,pretreatment with simvastatin can improve the degree significantly and maintain the adapta-bility to frequence basically. The protein expression levels of atrial α1c subunit of L-type calcium channel de-creased significantly after 8 hours pacing,pretreatment with simvastatin can prevent this change without lowering the lipid levels,thus contributing to the ionic mechanism of simvastatin for antiarrhythmia.