正丁基苯酞通过抑制心力衰竭大鼠心房重构降低心房颤动易感性  

N-butylphthalide reduces susceptibility to atrial fibrillation by inhibiting atrial structural remodeling in rats with heart failure

作　　者：刘洋[1] 梁潇 李晶瑾 郝翔 折剑青[1] LIU Yang;LIANG Xiao;LI Jingjin;HAO Xiang;SHE Jianqing(Department of Cardiovascular Medicine,First Affiliated Hospital of Xi’an Jiaotong University,Xi’an 710061,China)

机构地区：[1]西安交通大学第一附属医院心血管内科,西安710061

出　　处：《山西医科大学学报》2020年第8期766-773,共8页Journal of Shanxi Medical University

基　　金：国家自然科学基金青年科学基金项目(81800390)。

摘　　要：目的探究正丁基苯酞对大鼠心力衰竭中心房结构重构及房颤易感性的影响。方法将90只雄性Wistar大鼠随机分为3组:正丁基苯酞组、模型组和假手术组,每组30只。正丁基苯酞组和模型组大鼠结扎左前降支冠状动脉(LADCA)建立心肌梗死(MI)模型,然后进行房颤诱导。假手术组大鼠进行相同的手术,但不结扎LADCA。正丁基苯酞组大鼠按照每天200 mg/kg的剂量(2 ml)灌胃,模型组和假手术组用等量(2 ml)的大豆油灌胃。各组大鼠均给药4周,每天1次。采用Masson三色染色评估大鼠左心房组织纤维化,免疫组化检测左心房组织连接蛋白43(Cx43)的表达,蛋白质印迹分析大鼠左心房组织中collagenⅠ、collagenⅢ、α-平滑肌肌动蛋白(α-SMA)、肿瘤坏死因子-α(TNF-α)、肿瘤生长因子-β1(TGF-β1)、核因子-κB(NF-κB)、核因子E2相关因子2(Nrf2)和血红素加氧酶-1(HO-1)的表达。通过WST-1法检测大鼠血清超氧化物歧化酶(SOD)水平,可见光法检测过氧化氢酶(CAT)水平,TBA法检测丙二醛(MDA)水平。结果正丁基苯酞组大鼠的房颤诱导率显著低于模型组(P<0.05);正丁基苯酞组大鼠的房颤持续时间显著低于模型组(P<0.05)。与模型组相比,正丁基苯酞组大鼠左心房的纤维化和心肌细胞肥大明显减轻。正丁基苯酞组collagenⅠ、collagenⅢ和α-SMA的蛋白表达水平显著低于模型组(P<0.05)。与模型组相比,正丁基苯酞组大鼠的Cx43的阳性染色评分显著升高(1.13±0.15 vs 4.20±0.55,P<0.05)。正丁基苯酞组大鼠TNF-α、TGF-β1和NF-κB水平均显著低于模型组(P<0.05)。正丁基苯酞组大鼠Nrf2和HO-1蛋白表达水平均显著高于模型组(P<0.05)。正丁基苯酞组大鼠的SOD和CAT活性显著高于模型组,而MDA水平显著低于模型组(P<0.05)。结论正丁基苯酞通过抑制炎症反应、改善间隙连接重塑及激活Nrf2/HO-1介导的抗氧化活性降低心力衰竭大鼠的房颤易感性并抑制心房结构重�Objective To investigate the effects of n-butylphthalide on the structural remodeling and the susceptibility to atrial fibrillation in heart failure rats.Methods Ninety male Wistar rats were randomly divided into 3 groups(n=30 in each group),namely n-butylphthalide group,model group and sham group.The left anterior descending coronary artery(LADCA)was ligated to establish a myocardial infarction(MI)model in n-butylphthalide group and model group,and then the rats were given atrial fibrillation induction.Rats in sham group underwent the same operation without ligating LADCA.Rats were gavaged 2 ml n-butylphthalide solution at a dose of 200 mg/kg body weight per day in n-butylphthalide group,and equal amounts of soybean oil in model group and sham group.Rats in each group were administered once a day for 4 weeks.The left atrial fibrosis was assessed by Masson’s trichrome staining.The expression of connexin 43(Cx43)in left atrium tissue was assessed by immunohistochemistry.The expression of collagenⅠ,collagenⅢ,α-smooth muscle actin(α-SMA),tumor necrosis factor-α(TNF-α),tumor growth factor-β1(TGF-β1),nuclear factor-κB(NF-κB),nuclear factor E2-related factor 2(Nrf2)and heme oxygenase-1(HO-1)in the left atrium of rats were evaluated by Western blot.Serum superoxide dismutase(SOD),catalase(CAT)and malondialdehyde(MDA)levels were measured.Results The induction rate of atrial fibrillation was significantly lower in n-butylphthalide group than in model group(P<0.05).The duration of atrial fibrillation in n-butylphthalide group was significantly lower than in model group(P<0.05).Compared to model group,the fibrosis and the myocardial hypertrophy in the left atrium of rats in n-butylphthalide group were significantly alleviated.The protein expression levels of collagenⅠ,collagenⅢandα-SMA in n-butylphthalide group were significantly lower than those in model group(P<0.05).The positive staining score of Cx43 was significantly higher in n-butylphthalide group than in model group(1.13±0.15 vs 4.20±0.55,P<0.05

关 键 词：正丁基苯酞 心力衰竭 心房颤动 心房结构重塑 组织纤维化 大鼠 

分 类 号：R541.75[医药卫生—心血管疾病]