螺内酯在犬心房颤动模型中对心房结构重构及电重构的影响

Effect of spironolactone on atrial structural remodeling and electrical remodeling in the canine atrial fibrillation model

目的:观察螺内酯在犬心房颤动(房颤)模型中对心房结构重构和电重构的影响。方法:24只健康犬随机分为对照组(普通喂食)、房颤组(快速起搏+普通喂食)和螺内酯组(快速起搏+螺内酯灌胃),采用心房快速起搏建立犬房颤的动物模型。建模成功后,取左心房肌组织测定基质金属蛋白酶(MMP)-9、MMP组织抑制物(TIMP)-1以及miRNA-101水平,比较各组间以上指标的差异。结果:与对照组比较,房颤组和螺内酯组MMP-9、MMP-9/TIMP-1均显著升高(均P<0.01),房颤组TIMP-1降低(P<0.01),螺内酯组TIMP-1升高(P<0.01);与房颤组比较,螺内酯组MMP-9表达水平降低(P<0.05),TIMP-1表达水平升高(P<0.05),MMP-9/TIMP-1的比值降低(P<0.05)。房颤组miRNA-101较对照组及螺内酯组明显下调(P<0.05),而螺内酯组与对照组间未见显著差异。结论:快速心房起搏诱导房颤后可使心房肌出现电重构和结构重构,螺内酯干预可以上调miRNA-101,升高MMPs,降低TIMP,改善心房肌结构重构和电重构,从而起到预防和治疗房颤的作用。

Objective：To observe the effect of spironolactone on atrial structure remodeling and electrical remodeling in the canine atrial fibrillation model.Method：Twenty-four healthy adult dogs were selected and ran- domly divided into control group（n=8,normal feeding）,atrial fibrillation group（n=8,pacemaker implantation and normal feeding）and spironolactone group（n=8,pacemaker implantation and spironolactone intervention）. Pacemaker implantation and rapid atrial pacing were adopted to establish the canine atrial fibrillation model.After a week the model was successfully established and left atrial tissue was taken to determination the level of matrix metalloproteinase（MMP）-9,tissue inhibitor-1of MMP（TIMP-1）and miRNA-101.Then we compared the above indexes between different groups.Result：Compared to control group,the level of MMP-9,MMP-9/TIMP-1ratio were significantly higher in atrial fibrillation group and spironolactone group（both P〈0.01）,the level of TIMP- 1was significantly lower in atrial fibrillation group（P〈0.01）and was significantly higher in spironolactone group （P〈0.01）;Compared to atrial fibrillation group,the level of MMP-9in spironolactone group was lower（P 0.05）,the expression of TIMP-1was higher（P〈0.05）,the ratio of MMP-9/TIMP-1declined （P〈0.05）. Quantitative analysis showed that the miRNA-101in atrial fibrillation group obviously down-regulated compared with in control group and spironolactone group（both P〈0.05）,and it didn′t show statistically significant differ- ence between spironolactone group and control group.Conclusion：Atrial fibrillation caused by rapid atrial pacing could lead atrial structural remodeling and electrical remodeling.Spironolactone intervention could up-regulate miRNA-101,decrease MMP-9levels and elevate TIMP-1levels,which play a role of prevention and treatment for atrial fibrillation.