基质金属蛋白酶在肥厚心肌中的表达与过氧化物酶体增殖物活化受体γ激活剂的调控效应  

Expression of matrix metalloproteinase in hypertropic myocardium and the regulatory effect of peroxisome proliferator-activated receptor gamma activator

作　　者：杨维[1] 周新[1] 叶平[2] 伍仕敏[1] 刘永学[3] 

机构地区：[1]武汉大学中南医院基因诊断中心,湖北省武汉市430071 [2]解放军总医院老年心血管二科 [3]北京放射医学研究所药理毒理室,北京市100850

出　　处：《中国临床康复》2006年第40期40-43,共4页Chinese Journal of Clinical Rehabilitation

基　　金：国家自然科学基金(30270551);全军"十五"计划课题资助项目(02M012)~~

摘　　要：目的:观察过氧化物酶体增殖物活化受体γ激活剂吡格列酮对体外肥厚心肌细胞基质金属蛋白酶表达水平的影响。方法:实验于2005-04/12在军事医学科学院放射医学研究所药理毒理室完成。体外培养新生Wistar大鼠心肌细胞,以血管紧张素Ⅱ刺激建立心肌肥厚模型。将心肌细胞分为5组,即正常对照组、心肌细胞肥大模型组及吡格列酮5,10,20μmol/L组,其中肥大模型组仅诱导心肌细胞肥大,不加吡格列酮处理;吡格列酮5,10,20μmol/L组分别在加入血管紧张素Ⅱ前30min,培养液中加入不同浓度的吡格列酮(5,10,20μmol/L)处理;正常对照组不加血管紧张素Ⅱ。采用半定量反转录-聚合酶链反应法检测心肌肥厚特征性基因心钠肽、脑钠肽、基质金属蛋白酶2,9以及过氧化物酶体增殖物活化受体γmRNA的表达水平,通过测定3H-亮氨酸掺入量检测心肌细胞蛋白合成速率,并用软件分析心肌细胞表面积。结果:①与正常对照组相比,心肌细胞肥大模型组心肌细胞表面积增加了49%(P<0.01)、蛋白合成速率显著增加(P<0.01),心钠肽、脑钠肽、基质金属蛋白酶2,9的mRNA表达也显著增加(P<0.01),过氧化物酶体增殖物活化受体γ的mRNA表达显著下降(P<0.01)。②与心肌细胞肥大模型组相比,吡格列酮10μmol/L组心肌细胞的表面积减小了19%;吡格列酮5,10,20μmol/L组的蛋白合成速率及心钠肽、脑钠肽的mRNA表达均显著降低(P<0.05～0.01),并呈一定的剂量依赖性;吡格列酮5,20μmol/L组的基质金属蛋白酶2,9mRNA的表达均显著降低(P<0.05～0.01),过氧化物酶体增殖物活化受体γmRNA的表达显著增加(P<0.05～0.01),并呈一定的剂量依赖性。结论:吡格列酮能够抑制大鼠的心肌肥厚,这一作用可能与其增加过氧化物酶体增殖物活化受体γmRNA表达,下调基质金属蛋白酶表达有关。AIM： To explore the effect of peroxisome proliferator-activated receptor gamma （PPAR γ） activator pioglitazone on the expression of matrix metalloproteinase （MMP） in cardiac hypertrophy in vitro. METHODS： The experiment was performed at the Department of Pharmacology and Toxicology, Beijing Institute of Radiation Medicine, Academy of Military Medicine Science between April and December 2005. Myocardial cells of new-born Wistar rats were cultured in vitro. Models with cardiac hypertrophy was established with angiotensin Ⅱ stimulation. Myocardial cells-were assigned into 5 groups： normal control group, cardiac hypertrophy model group and 5,10,20 μmol/L pioglitazone groups. The cardiac hypertrophy model group only induced cardiac hypertrophy, pioglitazone. The 5,10,20 μ mol/L pioglitazone groups were exposed to pioglitazone at different concentration 30 minutes before adding angiotensin Ⅱ, respectively. Normal control group did not receive angiotensin Ⅱ. The mRNA expression of atrial natriuretic peptide （ANP）, brain natriuretic peptide （BNP）, matrix metalloproteinase 2, 9 （MMP-2, MMP-9） and PPARγ were examined with semi-quantitative reverse transcription-polymerase chain reaction （RT-PCR）. The synthetic rate of protein in myocardial cells was detected by ^3H-leucine incorporation. The surface area of myocardial cells was analyzed with software. RESULTS：（1） Compared with the normal control group, the surface area of myocardial cells increased by 49% （P 〈 0.01） in the cardiac hypertrophy model group; The synthetic rate of protein increased markedly （P 〈 0.01 ）; The mRNA expression of ANP, BNP, MMP-2 and MMP-9 also remarkably increased （P 〈 0.01）; The mRNA expression of PPARγ decreased obviously （P 〈 0.01 ）. （2） Compared with cardiac hypertrophy model group, the surface area of myocardial cells in the 10 μmol/L pioglitazone group decreased by 19%. The synthetic rate of protein and mRNA expression of ANP and BNP reduced distinctly in the 5,1

关 键 词：心肌病 肥大性 噻唑类/治疗应用 受体 金属蛋白酶类 

分 类 号：R542.2[医药卫生—心血管疾病]