Effects of febuxostat on atrial remodeling in a rabbit model of atrial fibrillation induced by rapid atrial pacing  

作　　者：Yong-Yan FAN Feng XU Chao ZHU Wen-Kun CHENG Jian LI Zhao-Liang SHAN Yang LI Yu-Tang WANG 

机构地区：[1]College of Medicine,Nankai University,Tianjin,China [2]Department of Cardiology,Chinese PLA General Hospital,Beijing,China [3]Department of Bone&Joint,Shijingshan Teaching Hospital of Capital Medical University,Beijing Shijingshan Hospital,Beijing,China [4]Department of Heart Center,Beijing Friendship Hospital,Capital Medical University,Beijing,China [5]Department of Geriatric Cardiology,Chinese PLA General Hospital,Beijing,China

出　　处：《Journal of Geriatric Cardiology》2019年第7期540-551,共12页老年心脏病学杂志（英文版）

基　　金：supported by the Beijing Natural Science Foundation(Z141100002114050)

摘　　要：Background Febuxostat,a novel nonpurine selective inhibitor of xanthine oxidase(XO),may be used in the prevention and management of atrial fibrillation(AF).The purpose of this study was to evaluate the effects of febuxostat on atrial remodeling in a rabbit model of AF induced by rapid atrial pacing(RAP)and the mechanisms by which it acts.Methods Twenty-four rabbits were randomly divided into four groups:sham-operated group(Group S),RAP group(Group P),RAP with 5 mg/kg per day febuxostat group(Group LFP),and RAP with 10 mg/kg per day febuxostat group(Group HFP).All rabbits except those in Group S were subjected to RAP at 600 beats/min for four weeks.The effects of febuxostat on atrial electrical and structural remodeling,markers of inflammation and oxidative stress,and signaling pathways involved in the left atrium were examined.Results Shortened atrial effective refractory period(AERP),increased AF inducibility,decreased mRNA levels of Cav1.2 and Kv4.3,and left atrial enlargement and dysfunction were observed in Group P,and these changes were suppressed in the groups treated with febuxostat.Prominent atrial fibrosis was observed in Group P,as were increased levels of TGF-β1,Collagen I,andα-SMA and decreased levels of Smad7 and eNOS.Treatment with febuxostat attenuated these differences.Changes in inflammatory and oxidative stress markers induced by RAP were consistent with the protective effects of febuxostat.Conclusions This study is the first to find that febuxostat can inhibit atrial electrical and structural remodeling of AF by suppressing XO and inhibiting the TGF-β1/Smad signaling pathway.Background Febuxostat, a novel nonpurine selective inhibitor of xanthine oxidase(XO), may be used in the prevention and management of atrial fibrillation(AF). The purpose of this study was to evaluate the effects of febuxostat on atrial remodeling in a rabbit model of AF induced by rapid atrial pacing(RAP) and the mechanisms by which it acts. Methods Twenty-four rabbits were randomly divided into four groups: sham-operated group(Group S), RAP group(Group P), RAP with 5 mg/kg per day febuxostat group(Group LFP), and RAP with 10 mg/kg per day febuxostat group(Group HFP). All rabbits except those in Group S were subjected to RAP at 600 beats/min for four weeks. The effects of febuxostat on atrial electrical and structural remodeling, markers of inflammation and oxidative stress, and signaling pathways involved in the left atrium were examined. Results Shortened atrial effective refractory period(AERP), increased AF inducibility, decreased m RNA levels of Cav1.2 and Kv4.3, and left atrial enlargement and dysfunction were observed in Group P, and these changes were suppressed in the groups treated with febuxostat. Prominent atrial fibrosis was observed in Group P, as were increased levels of TGF-β1, Collagen I, and α-SMA and decreased levels of Smad7 and eNOS. Treatment with febuxostat attenuated these differences. Changes in inflammatory and oxidative stress markers induced by RAP were consistent with the protective effects of febuxostat. Conclusions This study is the first to find that febuxostat can inhibit atrial electrical and structural remodeling of AF by suppressing XO and inhibiting the TGF-β1/Smad signaling pathway.

关 键 词：ATRIAL FIBRILLATION ATRIAL remodeling FEBUXOSTAT Rapid ATRIAL PACING XANTHINE OXIDASE 

分 类 号：R97[医药卫生—药品]