摘要
目的通过建立快速起搏兔心房模型,探讨miR-208a在心房电重构和结构重构中的作用。方法40只新西兰大耳白兔随机分为4组:假手术组(SHAM组)、快速起搏组(RAP组)、快速起搏+agomiR-208a组(miR-208a组)和快速起搏+antagomiR-208a组(antmiR-208a组),每组各10只。起搏频率为600次/min,在程序刺激的0、4、8、12 h测定心房有效不应期(AERP)并计算AERP频率适应性。刺激结束后,处死动物,收集左心房组织,检测超氧化物歧化酶(SOD)活性、丙二醛(MDA)、活性氧(ROS)水平评估氧化应激;HE染色观察心房结构重构;采用RT-PCR法检测miR-208a RNA表达;采用Western blot法检测β-catenin表达。结果RT-PCR显示,RAP组miR-208a水平均低于SHAM组和miR-208a组(均P<0.05);与RAP组相比,antmiR-208a组中miR-208a水平明显降低(P<0.05)。与RAP组相比,miR-208a组AERP明显改善,而antmiR-208a组的结果相反;与RAP组相比,miR-208a组的AERP频率适应性升高,而antmiR-208a组降低(P<0.05)。HE染色显示,RAP组心肌纤维排列不规则,部分纤维溶解并断裂,与RAP组比较,antmiR-208a组的心肌组织病理改变更加显著,而miR-208a组的心肌组织病理改变得到改善。与RAP组相比,miR-208a组心肌组织中MDA和ROS水平均降低,SOD活性升高(均P<0.05);antmiR-208a组的MDA和ROS水平均升高,SOD活性降低(均P<0.05)。Western blot显示,RAP组β-catenin蛋白表达高于SHAM组(P<0.05);与RAP组相比,miR-208a组中β-catenin蛋白表达降低,而antmiR-208a组升高(均P<0.05)。结论miR-208a可以改善心房快速起搏模型兔中心房的电重构和结构重构,并减轻心房的氧化应激水平,这些作用可能与β-catenin信号传导途径的抑制有关。
Objective A model was established to explore the preventative to investigate the effect and possible mechanism of miR-208a on the electrical and structural remodeling induced in rabbits with rapid atrial pacing.Methods Forty New Zealand white rabbits were randomly divided into sham operation group(SHAM group,n=10),rapid pacing group(RAP group,n=10),rapid pacing+agomiR-208a group(miR-208a group,n=10),and rapid pacing+antagomiR-208a group(antmiR-208a group,n=10).The pacing frequency was 600 beats/min,and procedural stimulation was performed at 0,4,8,and 12 h to determine the atrial effective refractory period(AERP)and the AERP frequency adaptability was calculated.The animals were sacrificed after stimulation,the samples of left atrial tissue were collected,and the activity of superoxide dismutase(SOD),level of malondialdehyde(MDA)and reactive oxygen species(ROS)were detected to evaluate the oxidative stress.The level of atrial structural remodeling was observed by HE staining,and the RNA expression of miR-208a in each group was detected by RT-PCR.The expression ofβ-catenin was detected by Western blot.Results RT-PCR showed that the expression of miR-208a in the RAP group was lower than that in the SHAM and miR-208a groups.Compared with the RAP group,the expression of miR-208a in the antmiR-208a group was significantly decreased(P<0.05).Compared with the RAP group,the AERP in the miR-208a group was significantly improved,while the antmiR-208a group exhibited the opposite results.Compared with the RAP group,the frequency adaptability of AERP200-150 in the miR-208a group was improved,while that in the antmiR-208a group was significantly decreased(P<0.05).Compared with the RAP group,the contents of MDA and ROS in the atrial muscle of the miR-208a group were significantly decreased and the activity of SOD was increased(all P<0.05);however,the contents of MDA and ROS in the antmiR-208a group were significantly higher and the activity of SOD was significantly lower than those in the RAP group(all P<0.05).HE staining sho
作者
徐孟骅
王忠华
王静
朱晓锋
李雯
李勇
XU Menghua;WANG Zhonghua;WANG Jing;ZHU Xiaofeng;LI Wen;LI Yong(Department of Cardiology,the First People's Hospital of Yuhang District,Hangzhou 311100,China;不详)
出处
《浙江医学》
CAS
2023年第16期1686-1692,共7页
Zhejiang Medical Journal
基金
杭州市医药卫生科技项目(B20231533)
杭州市科技计划引导项目(20201231Y151)。
关键词
房颤
快速起搏
心房有效不应期
氧化应激
Atrial fibrillation
Rapid pacing
Atrial effective refractory period
Oxidative stress
