阿托伐他汀对慢性兔房颤模型心房电重构的影响

Effects of atorvastatin on atrial electrical remodeling in a rabbit model of chronic atrial fibrillation

目的:通过快速起搏心房3周建立慢性兔房颤模型,探讨阿托伐他汀(ATO)对该模型心房电重构的影响及其可能机制。方法:将24只新西兰大白兔开胸,于左心房植入起搏和测试电极,随机分为3组:模型(model)组和ATO组持续心房起搏3周,分别给予安慰剂和阿托伐他汀2.5 mg·kg^(-1)·d^(-1)灌胃;假手术(sham)组不起搏,不给药。起搏前后用电生理刺激仪检测心率、P波宽度、心房有效不应期(AERP)和房颤诱发率的变化;起搏后采用Western blot检测心房Cav1.2、Kv4.3和髓过氧化物酶(MPO)的蛋白表达水平。结果:Sham组、model组和ATO组分别有0、5和4只兔诱发持续性房颤。起搏3周后,与sham组相比,model组和ATO组兔心率和P波宽度均增加,AERP缩短(P<0.05);ATO组与model组相比,AERP增加(P<0.05),心率和P波宽度无明显变化。与sham组相比,model组和ATO组兔心房Cav1.2和Kv4.3的蛋白表达水平下降,MPO的蛋白表达水平升高(P<0.05);ATO组与model组相比,Cav1.2的表达增加,MPO的表达下降(P<0.05),Kv4.3无明显变化。结论:阿托伐他汀能够通过抑制慢性兔房颤模型心房Cav1.2蛋白表达下降和AERP的缩短,抑制心房电重构,其潜在机制可能是阿托伐他汀抑制了心房MPO蛋白的高表达。

AIM：To evaluate the effects of atorvastatin（ATO）on atrial electrical remodeling in a rabbit model of chronic atrial fibrillation（AF）produced by 3 weeks of rapid atrial pacing（RAP）.METHODS：The sternotomy was performed and the pacing and testing electrodes were fixed to the left atria of 24 New Zealand white rabbits.The animals were randomly divided into 3 groups.The rabbits in model group and ATO group were subjected to RAP for 3 weeks,and then were treated with placebo and ATO（2.5 mg·kg-1·d-1）,respectively.The rabbits in sham group did not receive RAP and drugs.Electrophysiological examination was performed to test heart rate,P-wave duration,atrial effective refractory period（AERP）and AF inducibility.The protein expression levels of Cav1.2,Kv4.3 and myeloperoxidase（MPO）were detected by Western blot.RESULTS：Sustained AF was induced in 5 and 4 rabbilts in model group and atorvastatin group and no rabbits in sham group was found.After 3 weeks of RAP,compared with sham group,heart rate and P-wave duration were increased and AERP was shortened in model group and ATO group（P〈0.05）.Compared with model group,AERP was increased in ATO group（P〈0.05）,while heart rate and P-wave duration had no difference between these 2 groups.Compared with sham group,the protein levels of Cav1.2 and Kv4.3 were decreased,and protein level of MPO was increased in model group and ATO group（P〈0.05）.Compared with model group,Cav1.2 was increased and MPO was decreased in ATO group（P〈0.05）,while Kv4.3 had no difference between these 2 groups.CON-CLUSION：Atorvastatin suppresses the down-regulation of atrial Cav1.2 protein level and the shortening of AERP,thus preventing atrial electrical remodeling in a rabbit model of chronic AF.The effect of atrovastatin on reducing atrial MPO level may be the potential mechanism.