过表达c-Ski改善心房颤动犬模型心房电重构和结构重构  

Overexpression of c-Ski improves atrial electrical and structural remodeling in canine model of atrial fibrillation

作　　者：韩素霞 王娟[2] 高苏莉 盛乐智 李耀 HAN Suxia;WANG Juan;GAO Suli;SHENG Lezhi;LI Yao(Department of Cardiology,Pudong New Area Peoples′Hospital,Affiliated to Shanghai University of Medicine&Health Sciences,Shanghai 201200;Department of Cardiology,The Fifth Affiliated Hospital of Xinjiang Medical University,Urumchi 830001,China)

机构地区：[1]上海市浦东新区人民医院心内科,201200 [2]新疆医科大学第五附属医院心内科,乌鲁木齐830001

出　　处：《国际心血管病杂志》2021年第6期360-364,共5页International Journal of Cardiovascular Disease

基　　金：国家自然科学基金(81660044);浦东新区卫健委领先人才(PWRI2017-06);浦东新区科技发展基金(PKJ2017-Y35)。

摘　　要：目的:分析c-Ski对快速起搏诱导的心房颤动(AF)犬模型心房电重构和结构重构的作用。方法:将18只比格犬随机分为4组:假手术组(n=3)、AF对照组(n=3,仅构建AF模型)、AF-AdNull组(n=6,构建AF模型+注射AdNull腺病毒)及AF-Adc-Ski组(n=6,构建AF模型+注射Adc-Ski腺病毒)。采用电生理实验分析犬AF的诱发率及持续时间。应用苏木精-伊红染色、Masson法染色和天狼猩红染色评价诱导AF后的组织病理学改变。Western blot检测c-Ski、α-平滑肌肌动蛋白(α-SMA)和Ⅲ型胶原蛋白(collagenⅢ)在心房组织中的表达。结果:与假手术组相比,AF对照组和AF-AdNull组AF的诱发率明显上升,持续时间明显延长,心肌组织中c-Ski表达降低,α-SMA和collagenⅢ表达增加(P均<0.05),组织染色显示心肌细胞肥大、心肌细胞排列方向紊乱及心肌细胞间质纤维化和心肌纤维化严重;与AF对照组和AF-AdNull组相比,AF-Adc-Ski组AF的诱发率明显下降,持续时间明显缩短,心肌组织中c-Ski表达升高,α-SMA和collagenⅢ表达降低(P均<0.05),心房肌纤维分布相对整齐,排列大致有序,心肌间质纤维化以及纤维组织增生程度明显降低。结论:过表达c-Ski能够改善AF犬模型心房电重构和结构重构,c-Ski在AF相关心房重构中发挥重要作用。Objective:To analyze the effect of c-Ski on atrial electrical and structural remodeling induced by rapid atrial pacing in canine model of atrial fibrillation(AF).Methods:Eighteen beagles were randomly divided into four groups:sham surgery group(n=3),AF control group(n=3,AF model was constructed with no intervention),AF-AdNull group(n=6,AF model was constructed and then transfected adenovirus vector containing no transgene expression cassette)and AF-Adc-Ski group(n=6,AF model was constructed and then transfected adenovirus vector overexpressing c-Ski).The duration and inducibility of AF were analyzed by electrophysiological experiment.Hematoxylin-eosin staining,Masson trichromatic staining and picrosirius red staining were used to evaluate the histopathological changes induced by AF.Expression of c-Ski,α-smooth muscle actin(α-SMA)and collagenⅢin the atrial tissues were detected by western blot.Results:Compared with the sham surgery group,the inducibility and duration of AF were significantly increased in the AF control group and AF-AdNull group,while the expression level of c-Ski downregulated.Andα-SMA and collagenⅢexpression levels were increased in the atrial tissues of the AF control group and the AF-AdNull group(all P<0.05).The results of tissues staining showed that hypertrophy and disordered arrangement of cardiomyocytes,as well as fibrosis of interstitial cardiomyocytes were obvious in AF control group and AF-AdNull group.Compared with the AF control group and AF-AdNull group,the inducibility and duration of AF were significantly declined in the AF-Adc-Ski group,while the expression level of c-Ski upregulated.Andα-SMA and collagenⅢexpression levels were lower in the atrial tissues of the AF-Adc-Ski group(all P<0.05).The results of tissues staining showed that the distribution of atrial muscle fibers was relatively orderly,and the degree of myocardial interstitial fibrosis and fibrous tissue hyperplasia significantly reduced in the AF-Adc-Ski group.Conclusions:c-Ski could improve atrial electrical

关 键 词：心房颤动 心房重构 快速心房起搏 c-Ski 

分 类 号：R541.75[医药卫生—心血管疾病] R-332[医药卫生—内科学]