紫草素抑制ERK1/2-NF-κB通路对大鼠心房颤动的改善作用  

Effect of shikonin on improving atrial fibrillation of rats by inhibiting ERK1/2-NF-κB pathway

作　　者：舒礼良[1] 黄功成 郝爽 黄辰[1] 朱效华[1] 徐敬[1] Shu Li-Liang;Huang Gong-Cheng;Hao Shuang;Huang Chen;Zhu Xiao-Hua;Xu Jing(Department of Cardiovascular Surgery,the First Affiliated Hospital of Zhengzhou University,Zhengzhou 450052,China)

机构地区：[1]郑州大学第一附属医院心血管外科,郑州450052

出　　处：《解放军医学杂志》2021年第8期757-762,共6页Medical Journal of Chinese People's Liberation Army

基　　金：国家自然科学基金(81800319)。

摘　　要：目的探讨紫草素通过细胞外信号调节蛋白激酶1/2(ERK1/2)/核转录因子-κB(NF-κB)介导心肌细胞纤维化对大鼠心房颤动(简称房颤)的改善作用。方法30只SD大鼠随机分为正常对照组、模型组、紫草素组,每组10只。紫草素组大鼠以4 mg/kg紫草素灌胃给药,正常对照组和模型组大鼠等量生理盐水灌胃,1次/d,连续7 d;除正常对照组外,其余组大鼠按照1 ml/kg的剂量尾静脉注射乙酰胆碱-氯化钙(ACh-CaCl2)混合液1次/d、连续7 d建立房颤模型,正常对照组大鼠尾静脉注射等量生理盐水,7 d后取材。心电图检测各组大鼠房颤诱发时间和持续时间;超声心动图检测各组大鼠心功能;HE染色观察各组大鼠心肌组织病理学改变;Masson染色检测各组大鼠心肌组织胶原面积百分比;Western blotting检测各组大鼠胶原蛋白Ⅰ(ColⅠ)、ERK1/2、p-ERK1/2、NF-κB p65和p-NF-κB p65蛋白表达情况。结果正常对照组大鼠心肌细胞排列致密、整齐;模型组大鼠心肌细胞排列紊乱、肥大、间隙增宽;紫草素组大鼠心肌细胞形态和结构较模型组有所改善。与正常对照组比较,模型组及紫草素组大鼠左心室射血分数(LVEF)、左心室缩短分数(LVFS)降低,左心室收缩末期内径(LVESD)和左心室舒张末期内径(LVEED)增高,胶原面积百分比增加,ColⅠ、p-ERK1/2和p-NF-κB p65蛋白表达升高(P<0.05);与模型组比较,紫草素组大鼠房颤诱发时间延长、持续时间缩短,LVEF、LVFS升高,LVESD、LVEED缩短,胶原面积百分比减小,ColⅠ、p-ERK1/2和p-NF-κB p65蛋白表达明显降低(P<0.05)。结论紫草素可能通过抑制ERK1/2-NF-κB信号通路而减轻心肌纤维化,抑制房颤的发生,并改善心功能。Objective To investigate the effect of shikonin on atrial fibrillation of rats with myocardial fibrosis mediated by extracellular signal-regulated protein kinase1/2(ERK1/2)/nuclear transcription factor-kappaB(NF-κB).Methods Thirty SD rats were randomly divided into normal control group,model group,shikonin group(10 each).Rats in shikonin group were intragastrically given shikonin 4 mg/kg,in normal control and model groups were given the same amount of normal saline,1 time/d for consecutive 7 days;Rats in model and shikonin groups were tail intravenous injected with 1 ml/kg ACh-CaCl2 mixed liquor to establish atrial fibrillation model,1 time/d for consecutive 7 days,and in normal control group were injected with the same amount of normal saline,taken materials after 7 days.Electrocardiogram was used to record the induced time and duration of atrial fibrillation,and the cardiac function was detected by echocardiography.The pathological condition of myocardial tissue was observed by HE staining.Masson staining was performed to detect the percentage of collagen area in myocardial tissue.The protein expressions of CollagenⅠ(ColⅠ),ERK1/2,p-ERK1/2,NF-κB p65 and p-NF-κB p65 were detected by Western blotting.Results The cardiomyocytes were arranged in compact and orderly manner in normal control group,while in model group were disordered,hypertrophic and widened.Shikonin improved the morphology and structure of cardiomyocytes.Compared with normal control group,left ventricular ejection fraction(LVEF)and left ventricular fractional shortening(LVFS)decreased,left ventricular end-diastolic diameter(LVEDD),left ventricular end-systolic diameter(LVESD),percentage of collagen area,the expressions of ColⅠ,p-ERK1/2,p-NF-κB p65 protein increased(P<0.05)in model group and shikonin group;Compared with model group,the induced time of atrial fibrillation was longer,duration time was shorter in shikonin group,LVEF and LVFS increased,LVESD and LVEED,percentage of collagen area,and the expressions of ColⅠ,p-ERK1/2,p-NF-κB p6

关 键 词：心房颤动 紫草素 纤维化 细胞外信号调节蛋白激酶1/2 核转录因子-ΚB 

分 类 号：R541.7[医药卫生—心血管疾病]