心肌肥厚大鼠细胞外基质重塑中基质金属蛋白酶的作用及氯沙坦干预的效果(英文)  

Role of metalloproteinases in cardiac extracellular matrix remodeling in rats and effect of Losartan on it

作　　者：白江涛[1] 陆凤翔[1] 许迪[1] 陈莉[1] 周蕾[1] 雍永宏[1] 

机构地区：[1]南京医科大学第一附属医院心脏科,江苏省南京市210029

出　　处：《中国临床康复》2004年第15期2998-3000,共3页Chinese Journal of Clinical Rehabilitation

摘　　要：背景:细胞外基质中的纤维性胶原过度沉积是心肌肥厚发展过程中的重要特征。基质金属蛋白酶(matrixmetalloproteinases,MMPs)及其生理性抑制剂(tissueinhibitorofmetalloproteinases,TIMPs)是调节细胞外基质的重要酶类,转化生长因子β1(transforminggrowthfactor-β1,TGF-β1)能促进组织纤维化。目的:探讨MMP-9及其生理性抑制剂TIMP-1和TGF-β1在心肌肥厚大鼠细胞外基质重塑中的作用及氯沙坦干预的效果。设计:随机对照实验研究。地点、材料和干预:南京医科大学动物实验中心雄性SD大鼠随机用随机数字表法分为3组:对照组、去甲肾上腺素组犤1.06mg/(kg·d)×15d犦、去甲肾上腺素+氯沙坦组犤10mg/(kg.d)×15d犦。去甲肾上腺素腹腔注射,2次/d,连续15d,建立心肌肥厚的模型。氯沙坦灌胃给药。主要观察指标:腹腔注射生理盐水、去甲肾上腺素、氯沙坦灌胃给药大鼠超声心动图检查,病理检查,心肌胶原蛋白表达,MMP-9,TIMP-1和TGF-β1mRNA和蛋白表达情况的对比结果。结果:大鼠腹腔注射去甲肾上腺素后发生左心室肥厚及纤维化,胶原的含量及MMP-9(82.9±18.3),TIMP-1(43.8±7.3)和TGF-β1(49.4±7.9),mRNA的表达显著高于健康对照组。氯沙坦能降低室间隔的厚度,减少左室心肌中总体胶原、I型、III型胶原的合成及MMP-9。BACKGROUND: A disproportionate accumulation of fibrillar collagen is a chief c haracteristic of left ventricular hypertrophy. Matrix metalloproteinase (MMPs) a nd tissue inhibitor of metalloproteinase(TIMPs) are the most important regulator s of extracellular matrix, and transforming growth factor-β1(TGF-β1) can ind uce fibrosis. OBJECTIVE: To investigate the role of MMP-9, TIMP-1 and TGF-β1 in cardiac hypertrophy and extracellular matrix remodeling and effect of Losartan on it in rat model. DESIGN: A randomized controlled experimental study. SETTING, PARTICIPANTS and INTERVENTIONS: Male SD rats from Animal Center of Na njing Medical University were randomly divided into three groups: control, norep inephrine [1.06 mg/(kg·d)×15 d], and norepinephrine+Losartan [10 mg/(kg·d)× 15 d] groups. The rat models of cardiac hypertrophy were established by intraper itoneal injection of norepinephrine twice a day for 15 days. Losartan was given by gastric perfusion. MAIN OUTCOME MEASURES:Cardiac hypertrophy and extracellular matrix remodeling were evaluated by echocardiography and morphological examination.The mRNA and pr otein expression of matrix metalloproteinase (MMP-9) and tissue inhibitor of me talloproteinase(TIMP-1) and transforming growth factor-β1(TGF-β1) were exam ined by reverse transcription-polymerase chain reaction(RT-PCR) and immunohist ochemical analysis. RESULTS: NE-induced hypertrophy and extracellular matrix remodeling predomina ntly occurred on the left ventricular, and the mRNA and protein expression of MM P-9 (82.9±18.3), TIMP-1 (43.8±7.3), and TGF-β1 (49.4±7.9) were significan tly higher than those in the control group. After treatment of Losartan, the int erventricular septal thickness, total collagen, type I and type III collagens an d the expression of MMP-9 and TGF-β1 were decreased (P< 0.01). CONCLUSION: MMP-9, TIMP-1 and TGF-β1 are related to cardiac extracellular matrix remodeling induced by NE. Losartan can prevent cardiac hypertrophy and ex tracellular matrix remod

关 键 词：心肌肥厚 大鼠 细胞外基质 基质金属蛋白酶 氯沙坦 药物治疗 

分 类 号：R542.2[医药卫生—心血管疾病]