环维黄杨星D抑制房颤犬心房结构重塑中的作用  

Inhibitory Effect of Cyclovirbuxine-D on Atrial Structural Remodeling in Atrial Fibrillation Canines Model with Long-Term Atrial Pacing

作　　者：邱承杰[1] 毛文峰 王贺[1] 董文杰[1] 陈玉善[1] 关怀敏[1] 解金红[1] QIU Cheng-jie;MAO Wen-feng;WANG He;DONG Wen-jie;CHEN Yu-shan;GUAN Huai-min;XIE Jin-hong(Cardiovascular Department,the First Affiliated Hospital of Henan University of Chinese Medicine,Zhengzhou,450000;The First Clinical Medical College of Henan University of Chinese Medicine,Zhengzhou,450000)

机构地区：[1]河南中医药大学第一附属医院心内科,郑州450000 [2]河南中医药大学第一临床医学院,郑州450000

出　　处：《中国中西医结合杂志》2022年第6期722-727,共6页Chinese Journal of Integrated Traditional and Western Medicine

基　　金：国家自然科学基金资助项目(No.81473508)。

摘　　要：目的探讨环维黄杨星D(CVB-D)抑制房颤犬心房结构重塑中的作用。方法18只比格犬随机分为对照组(CL)、假手术组(Sham)、房颤组(AF)、房颤加胺碘酮组(AF+AD)、房颤加环维黄杨星-D组(AF+CVB-D)及房颤加普罗布考组(AF+PB),每组3只。采用快速起搏心房4周建立房颤动物模型。彩超检查起搏前后犬心脏左房上下径(LAD)、左室舒张末内径(LVDd)及左室射线分数(LVEF)。HE染色观察心肌组织及间质变化;ELISA法检测血清肿瘤坏死因子α(TNF-α)、Ⅰ型胶原蛋白(ColⅠ)、ColⅢ及赖氨酰氧化酶样蛋白2(LOXL-2)水平变化;Western Blot法检测左房心肌组织内肾素-血管紧张素系统相关的c3肉毒杆菌毒素底物1(Rac-1)蛋白表达量。结果起搏4周后,心肌细胞HE染色结果显示AF组心房肌细胞较CL组结构紊乱,细胞间隙增大,结构不完整。与本组起搏前比较,起搏4周后AF组LAD与LVDd增高(P<0.05),LVEF降低(P<0.05),血清TNF-α、ColⅠ、ColⅢ水平升高(P<0.05)。起搏4周后,分别与CL、Sham组比较,AF组LAD、LVDd、TNF-α、ColⅠ、ColⅢ、LOXL-2水平和心肌Rac-1蛋白表达升高,LVEF降低(P<0.05)。与AF组比较,AF+AD、AF+CVB-D及AF+PB组LAD、血清TNF-α、ColⅠ、ColⅢ、LOXL-2水平和心肌Rac-1蛋白表达降低,LVEF升高(P<0.05)。与AF+CVB-D组比较,AF+AD及AF+PB组血清LOXL-2水平升高(P<0.05)。结论CVB-D可以通过抑制炎症反应,调控细胞外基质纤维化关键过程,预防心房纤维化的发生及结构重塑。Objective To investigate the inhibitory effect of cyclovirbuxine-D(CVB-D)on atrial structural remodeling in atrial fibrillation canines model with long-term atrial pacing.Methods Eighteen beagles were randomly divided into control group(CL),atrial fibrillation group(AF),sham-operated group(Sham),AF+amiodarone group(AF+AD),AF+CVB-D group(AF+CVB-D),and AF+probucol group(AF+PB).Atrial fibrillation model was established by rapid pacing of atria for 4 weeks.The changes of left atrial inferior diameter(LAD),left ventricular end diastolic diameter(LVDd),and left ventricular ejection fraction(LVEF)were detected by transthoracic echocardiographic examination.Myocardial tissue and interstitial changes were detected by HE staining.The serum concentrations of tumor necrosis factor(TNF-α),collagenⅠ(ColⅠ),ColⅢand lysyl oxidase-like-2(LOXL-2)were detected by ELISA.The expression of Ras-related C3 botulinum toxin substrate1(Rac-1)protein in left atrial myocardium was detected by Western Blot.Results After four weeks pacing,HE staining of cardiomyocytes showed that compared with the CL group,the atrial myocytes in the AF group have a disordered structure,with enlarged intercellular spaces and incomplete structure.Compared with before pacing,LAD,LVDd,TNF-α,ColⅠ,ColⅢ,LOXL-2 levels and Rac-1 expression increased,while LVEF level decreased in the AF group(P<0.05).Compared with CL and Sham group,LAD,LVDd,TNF-α,ColⅠ,ColⅢ,LOXL-2 levels,and Rac-1 expression increased,LVEF level decreased in AF group(P<0.05).Compared with AF group,the levels of LAD,TNF-α,ColⅠ,ColⅢ,LOXL-2,and Rac-1 expression in AF+AD,AF+CVB-D and AF+PB groups were significantly decreased,while LVEF level increased(P<0.05).Compared with AF+CVB-D group,the LOXL-2 level in AF+AD and AF+PB groups increased(P<0.05).Conclusion CVB-D can prevent the occurrence and structural remodeling of atrial fibrosis by inhibiting the inflammatory response and regulating the key process of extracellular matrix fibrosis.

关 键 词：心房颤动 纤维化 环维黄杨星D 犬 结构重塑 

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