氨氯地平对肾性高血压大鼠心肌重构的影响  

Effects of amlodipine on myocardial remodeling in renal hypertensive rats

作　　者：夏哲林 周彬[2] 叶鑫[3] 章欣[1] XIA Zhe-lin;ZHOU Bin;YE Xin;ZHANG Xin(Department of Pharmacy,Taizhou Central Hospital,Affiliated Hospital of Taizhou University,Taizhou 318000,Zhejiang Province,China;Department of Pharmacy,the First Affiliated Hospital of Wenzhou Medical University,Wenzhou 325000,Zhejiang Province,China;Department of Pharmacy,Quzhou People’s Hospital,Quzhou 324000,Zhejiang Province,China)

机构地区：[1]台州市中心医院、台州学院附属医院药剂科,浙江台州318000 [2]温州医科大学附属第一医院药学部,浙江温州325000 [3]衢州市人民医院药学部,浙江衢州324000

出　　处：《中国临床药理学杂志》2021年第16期2194-2197,共4页The Chinese Journal of Clinical Pharmacology

摘　　要：目的研究氨氯地平对肾性高血压大鼠心肌重构及p38丝裂原活化蛋白激酶(p38MAPK)/激活蛋白-1(AP-1)信号通路的影响。方法将40只肾性高血压大鼠随机分为模型组(n=20)与实验组(n=20),另选20只大鼠仅分离左肾动脉作为假手术组。实验组大鼠灌胃10 mg·kg^(-1)·d^(-1)氨氯地平,每天1次,模型组与假手术组灌胃等量生理盐水,每天1次,连续干预10周。用超声诊断仪检测左心室舒张末期内径(LVEDD)、左心室收缩末期内径(LVESD)、左心室舒张末期后壁厚度(LVPWD)、舒张末期室间隔厚度(IVSD),并计算左心室射血分数(LVEF)与短轴缩短率(LVFS);用苏木精-伊红(HE)染色观察大鼠心肌组织病理学变化;用酶联免疫吸附(ELISA)法检测心肌组织血管紧张素Ⅱ(AngⅡ)、醛固酮(ALD)与心钠素(ANP)含量;用蛋白质印迹(WB)法检测心肌组织磷酸化p38MAPK(p-p38MAPK)、AP-1蛋白的表达水平。结果假手术组、模型组与实验组大鼠LVEDD分别为(0.56±0.08),(0.89±0.06),(0.63±0.03)mm;LVESD分别为(2.01±0.09),(3.92±0.13),(3.06±0.11)mm;LVPWD分别为(0.13±0.01),(0.39±0.05),(0.22±0.04)cm;IVSD分别为(0.15±0.01),(0.34±0.03),(0.23±0.02)cm;LVEF分别为(74.21±2.17)%,(56.83±1.84)%,(63.43±2.39)%;LVFS分别为(47.32±2.36)%,(24.11±1.61)%,(41.06±1.18)%。与假手术组比较,模型组大鼠LVEDD、LVESD、LVPWD、IVSD与心肌组织AngⅡ、ALD、ANP含量及心肌组织p-p38MAPK、AP-1蛋白相对表达量均升高,且与模型组比较,实验组降低;而模型组LVEF与LVFS较假手术组降低,且与模型组比较,实验组升高(均P<0.05)。结论氨氯地平可有效改善肾性高血压大鼠心肌重构,进而改善心脏功能,其作用机制可能与抑制心肌组织p38MAPK/AP-1通路的信号转导相关。Objective To investigate the effects of amlodipine on myocardial remodeling and p38 mitogen activated protein kinase(p38 MAPK)/activator protein-1(AP-1) signaling pathway in renal hypertensive rats. Methods Forty renovascular hypertensive rats were randomly divided into model group(n=20) and experimental group(n=20). Another 20 rats were selected to seperate the left renal artery as sham operation group. Rats in experimental group were given 10 mg·kg-1·d-1 amlodipine, once a day by gavage, rats in model group and sham operation group were given the same amount of normal saline,once a day by gavage for 10 weeks. Left ventricular end diastolic diameter( LVEDD),left ventricular end systolic diameter( LVESD),left ventricular posterior wall thickness( LVPWD) and end diastolic interventricular septal thickness( IVSD) were measured by ultrasonic diagnostic instrument,and left ventricular ejection fraction( LVEF)and left ventricular fraction shortening( LVFS) were calculated;the pathological changes of myocardial tissue were observed by hematoxylin eosin( HE) staining;the contents of angiotensinⅡ( AngⅡ),aldosterone( ALD) and atrial natriuretic peptide( ANP) in myocardial tissue were detected by enzyme-linked immunosorbent assay( ELISA),and the expression levels of phosphorylated p38 MAPK and AP-1 protein in myocardial tissue were detected by Western blot. Results The LVEDD of sham operation group,model group and experimental group were( 0. 56 ± 0. 08),( 0. 89 ± 0. 06),( 0. 63 ± 0. 03) mm,LVESD were( 2. 01 ± 0. 09),( 3. 92 ± 0. 13),( 3. 06 ± 0. 11) mm,LVPWD were( 0. 13 ± 0. 01),( 0. 39 ± 0. 05),( 0. 22 ± 0. 04) cm, IVSD were( 0. 15 ± 0. 01),( 0. 34 ± 0. 03),( 0. 23 ± 0. 02) cm, LVEF were( 74. 21 ± 2. 17) %,( 56. 83 ± 1. 84) %,( 63. 43 ± 2. 39) %, LVFS were( 47. 32 ± 2. 36) %,( 24. 11 ± 1. 61) %,( 41. 06 ± 1. 18) %. Compared with sham operation group,the contents of LVEDD,LVESD,LVPWD,IVSD,Ang Ⅱ,ALD,ANP and the relative expressions of p-p38 MAPK and AP-1 in myocardial tissue of model group were inc

关 键 词：肾性高血压 氨氯地平 心肌重构 P38丝裂原活化蛋白激酶 激活蛋白-1 

分 类 号：R972[医药卫生—药品]