Vericiguat对Ach-CaCl_(2)诱导的房颤大鼠心肌纤维化的影响及机制研究  

Effects of Vericiguat on myocardium fibrosis in Ach-CaCl_(2) induced atrial fibrillation rats and its mechanism

作　　者：李丹[1] 林红 李璐依霏 段小旭 林宏 LI Dan;LIN Hong;LI Luyifei;DUAN Xiaoxu;LIN Hong(Cardiovascular Intensive Care Unit,The First Affiliated Hospital of Harbin Medical University,Harbin 150000,China;Cardiovascular Department,Harbin Chest Hospital,Harbin 150000,China)

机构地区：[1]哈尔滨医科大学附属第一医院心血管内科重症监护室,黑龙江哈尔滨150000 [2]哈尔滨市胸科医院心血管内科,黑龙江哈尔滨150000

出　　处：《西部医学》2025年第3期321-326,共6页Medical Journal of West China

基　　金：黑龙江省卫健委科研课题(20230303010066)。

摘　　要：目的探讨维利西呱(Vericiguat)对乙酰胆碱-氯化钙(Ach-CaCl_(2))诱导的房颤(AF)大鼠心肌纤维化的影响及其作用机制。方法将40只SD大鼠随机分为假手术组(sham组)、AF组、AF+Vericiguat组和AF+Vericiguat+SRI-011381(TGF-β信号通路激活剂)组,每组10只。采用尾静脉注射Ach-CaCl_(2)混合溶液制备AF大鼠模型,造模成功后AF+Vericiguat组和AF+Vericiguat+SRI-SRI-011381组相应给予Vericiguat和SRI-011381干预,sham组和AF组给予等量溶剂。心电图记录大鼠AF持续时间;HE、Masson染色检测大鼠心肌组织损伤和纤维化程度;碱水解法检测大鼠心肌组织中羟脯氨酸(Hyp)水平;免疫组化检测心肌组织中Ⅰ型胶原蛋白(collagenⅠ)和Ⅲ型胶原蛋白(collagenⅢ)表达;Western blot检测心肌组织中转化生长因子β1(TGF-β1)、p-Smad2、Smad2、p-Smad3、Smad3蛋白表达水平。结果与sham组比较,AF组大鼠心肌组织损伤和纤维化严重;AF持续时间和心肌组织中Hyp水平显著增加(P<0.05);心肌组织中collagenⅠ、collagenⅢ及TGF-β1蛋白和p-Smad2/Smad2、p-Smad3/Smad3水平显著升高(P<0.05)。与AF组比较,AF+Vericiguat组大鼠心肌组织损伤和纤维化程度明显减轻;AF持续时间和心肌组织中Hyp水平显著降低(P<0.05);心肌组织中collagenⅠ、collagenⅢ及TGF-β1蛋白和p-Smad2/Smad2、p-Smad3/Smad3水平显著降低(P<0.05)。联合SRI-011381干预能显著抑制Vericiguat对AF大鼠心肌组织纤维化的改善作用。结论Vericiguat可改善Ach-CaCl_(2)诱导的AF大鼠心肌纤维化,其作用机制可能是通过抑制TGF-β信号通路转导实现的。Objective To investigate the effect of Vericiguat on myocardium fibrosis induced by Ach-CaCl_(2) in rats with atrial fibrillation(AF)and its mechanism.Methods Forty SD rats were randomly divided into sham group,AF group,AF+Vericiguat group and AF+Vericiguat+SRI-011381(an activator of TGF-β signaling pathway)group,with 10 rats in each group.The AF rat model was prepared by injecting Ach-CaCl_(2) mixed solution into the tail vein.After successful modeling,Vericiguat and SRI-011381 were given intervention,and the same amount of vehicle was given to sham group.The duration of AF was recorded by electrocardiogram.HE and Masson staining were used to detect myocardial tissue injury and fibrosis.The level of hydroxyproline(Hyp)in myocardial tissue was detected by alkaline hydrolysis method.Immunohistochemistry was used to detect the expression of collagen Ⅰ and collagen Ⅲ in myocardial tissue.The protein expression levels of transforming growth factor-β1(TGF-β1),p-Smad2,Smad2,p-Smad3 and Smad3 in myocardial tissue were detected by western blot.Results Compared with sham group,the AF group exhibited more severe myocardial tissue damage and fibrosis in rats,the AF duration and Hyp level in myocardial tissue were significantly increased(P<0.05),and the protein expression levels of collagen Ⅰ,collagen Ⅲ,TGF-β1,p-Smad2/Smad2 and p-Smad3/Smad3 in myocardial tissue were significantly increased(P<0.05).Compared with AF group,the degree of myocardial tissue injury and fibrosis in AF+Vericiguat group was significantly reduced,the AF duration and Hyp level in myocardial tissue were significantly decreased(P<0.05),the protein expression levels of collagen Ⅰ,collagen Ⅲ,TGF-β1,p-Smad2/Smad3 and p-Smad3/Smad3 in myocardial tissue were significantly decreased(P<0.05).However,combined intervention with SRI-011381 could significantly inhibit the improvement of Vericiguat on myocardial fibrosis of AF rats.Conclusion Vericiguat can ameliorate Ach-CaCl_(2) induced myocardial fibrosis in AF rats,the mechanism of which may be

关 键 词：维利西呱 乙酰胆碱-氯化钙 房颤 纤维化 TGF-Β信号通路 

分 类 号：R541.75[医药卫生—心血管疾病]