基质金属蛋白酶在心肌肥厚大鼠细胞外基质重塑中的作用及氯沙坦干预.docVIP

基质金属蛋白酶在心肌肥厚大鼠细胞外基质重塑中的作用及氯沙坦干预 作者：白江涛 陆凤翔 许迪 陈莉 周蕾 雍永宏 【关键词】 心肌肥厚 　　Role of metalloprotEinases in rat cardiac extracellular matrix remodeling and effects of losartan on it 　　【Abstract】 AIM: To investigate the role of metalloprotEInase (MMP9), tissue inhibitor of metalloproteinase (TIMP1) and transforming growth factorβ1 (TGFβ1) in cardiac hypertrophy and extracellular matrix remodeling and the effects of Losartan on it in a rat model. METHODS: Male SD rats were randomly divided into three groups: control group, norepinephrine group (1.06 mgkg-1d-1?5 d) and norepinephrine + Losartan group (10 mgkg-1d-1?5 d). The rat cardiac hypertrophy models were established by intraperitoneal injection of norepinephrine (NE) twice a day for 15 days. Cardiac hypertrophy and extracellular matrix remodeling were evaluated by echocardiography and morphological examination. The mRNA and protein expression of matrix metalloproteinase (MMP9), tissue inhibitor of metalloproteinase (TIMP1) and transforming growth factorβ1 (TGFβ1) was examined by reverse transcriptionpolymerase chain reaction (RTPCR) and immunohistochemical analysis. RESULTS: NEinduced hypertrophy and extracellular matrix remodeling predominantly occurred in the left ventricular and the mRNA and protein expression of the MMP9, TIMP1 and TGFβ1 elevated (P0.01). After Losartan treatment, the interventricular septal thickness, total collagen, type I, type III collagen and the expression of MMP9 and TGFβ1 decreased (P0.01). CONCLUSION: MMP9, TIMP1 and TGFβ1 are involved in the cardiac extracellular matrix remodeling induced by NE. Losartan can prevent the cardiac hypertrophy and extracellular matrix remodeling, which is associated with the attenuation of myocardial MMP9 and TGFβ1. 　　【Keywords】 cardiac hypertrophy; extracellular matrix; metalloproteinase; Losartan 　　【摘要】 目的： 探讨基质金属蛋白酶(MMP9)及其生理性抑制剂TIMP1和转化生长因子β1（TGFβ1）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. 方法 ： 雄性SD大鼠随机分为3组：①对照组;②去甲肾上腺素(norepinephrine, N