| | | 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
| | 医学论文 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 mg・kg-1・d-1×15 d) and norepinephrine + Losartan group (10 mg・kg-1・d-1×15 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 (P<0.01). After Losartan treatment, the interventricular septal thickness, total collagen, type I, type III collagen and the expression of MMP9 and TGFβ1 decreased (P<0.01). 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】 目的医学论文： 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医学论文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, NE)组（1.06 mg・kg-1・d-1×15 d）;③NE+氯沙坦组（10 mg・kg-1・d-1×15 d）. NE腹腔注射，2次・d-1，连续15 d，建立心肌肥厚的模型. 应用超声心动图及病理学方法评价整体心肌肥厚和组织胶原的表达. 用逆转录聚合酶链反应法（RTPCR）及免疫组化方法检测MMP9, TIMP1和TGFβ1 mRNA和蛋白表达情况. 结果：大鼠腹腔注射NE后发生左心室肥厚及纤维化，胶原的含量及MMP9, TIMP1和TGFβ1的蛋白、mRNA的表达显著高于健康对照组（P<0.01）. 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MMP9,TGFβ1的表达（P<0.01）. 结论： MMP9, TIMP1和TGFβ1与NE诱导的心肌细胞外基质重塑有关. 氯沙坦能有效的防治心肌肥厚及细胞外基质重塑,这一效应与其降低心肌中高表达的MMP9和TGFβ1有关.
【关键词】 心肌肥厚；细胞外基质；基质金属蛋白酶；氯沙坦
0引言
基质金属蛋白酶（metalloproteinases, MMPs）是一类包含锌离子的内源性蛋白水解酶，是细胞外基质（ECM）的主要生理调节因子. 最近研究发现，MMPs在心梗后心衰的发病机制中具有重要的作用［1］. 转化生长因子β１（TGFβ1）被证实能促进组织纤维化和ECM积聚［２，３］. 有关延缓或防止心肌重塑的发展及其相关机制的研究，一直是心血管领域的热点. 我们旨在探讨MMP9及其生理性抑制剂TIMP1和TGFβ1在大鼠心肌肥厚及细胞外基质重塑过程中的作用及氯沙坦的防治作用.
1材料和方法
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