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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,TGF-β
BACKGROUND: Overexpression of fibrillar collagen in extracellular matrix is an important feature in the development of cardiac hypertrophy. Matrix metalloproteinases (MMPs) and their tissue inhibitors of metalloproteinases (TIMPs) are important enzymes that regulate the extracellular matrix. Transforming growth factor β1 (TGF-β1) promotes tissue fibrosis. AIM: To investigate the role of MMP-9 and its physiological inhibitors TIMP-1 and TGF-β1 in the extracellular matrix remodeling of cardiac hypertrophy in rats and the effect of losartan intervention. Design: Randomized controlled trial. Location, Materials and Intervention: Male SD rats of Animal Experiment Center of Nanjing Medical University were randomly divided into 3 groups: control group, norepinephrine group 犤 1.06mg / (kg · d) × 15d 犦, Epinephrine + losartan group 犤 10mg / (kg.d) × 15d 犦. Norepinephrine intraperitoneal injection, 2 times / d, continuous 15d, establishing a model of cardiac hypertrophy. Losartan gavage. MAIN OUTCOME MEASURES: Echocardiography, pathological examination, myocardial collagen expression, MMP-9, TIMP-1 and TGF-β1 mRNA and protein expression in rats intraperitoneally injected with normal saline, norepinephrine, losartan intragastric administration Comparison of the situation results. RESULTS: Left ventricular hypertrophy, fibrosis, collagen content and the expressions of MMP-9 (82.9 ± 18.3), TIMP-1 (43.8 ± 7.3) and TGF-β1 (49.4 ± 7.9) were observed in rats after intraperitoneal injection of norepinephrine mRNA expression was significantly higher than the healthy control group. Losartan can reduce the thickness of ventricular septum and reduce the synthesis of total collagen, type I and type III collagen and the expression of MMP-9 and TGF-β in left ventricular myocardium