氟伐他汀对心衰大鼠基质金属蛋白酶、转化生长因子及左室重构的影响  

Influence of fluvastatin on MMP-2, TGF-β_1 and left ventricular remodeling in rats with heart failure

作　　者：马静[1] 王虹[1] 哈黛文[1] 徐江[2] 

机构地区：[1]武汉大学中南医院综合医疗科 [2]武汉大学医学院老年病研究所生理系

出　　处：《中国临床药理学与治疗学》2004年第11期1243-1247,共5页Chinese Journal of Clinical Pharmacology and Therapeutics

摘　　要：目的:了解基质金属蛋白酶-2(MMP-2)及转化生长因子-β1(TGF-β1)在心肌梗死大鼠左室重构及心衰发展过程中的改变,以及氟伐他汀的干预作用,探讨心梗后心衰的发生机制。方法:选用雄性SD大鼠67只随机分为假手术组、心梗组和心梗他汀组,经冠状动脉前降支结扎术建立心肌梗死后心衰模型,手术24 h后心梗他汀组大鼠管饲氟伐他汀4 mg·kg-1·d-1,假手术组和心梗组大鼠管饲安慰剂。术后3 d、4周、8周检测大鼠非梗死区心肌MMP-2的含量(Western-blot法)、胶原、TGF-β1的改变(免疫组化法),压力传感器记录左室血流动力学改变。结果:术后各时点非梗死区心肌的MMP-2含量,心梗组及心梗他汀组显著高于假手术组(P<0.05),而心梗他汀组显著低于心梗组(P<0.05);术后各组各时点非梗死区心肌TGF-β1表达的变化趋势与MMP-2相同;与心梗组比较,心梗他汀组术后4周和8周的心功能明显改善,胶原容积分数(CVF)及Ⅰ／Ⅲ型胶原比值(Ratio of type Ⅰ／Ⅲ)降低(P<0.05)。结论:氟伐他汀通过减少非梗死区心肌MMP-2和TGF-β1的含量,而减轻心梗后非梗死区心肌胶原网络的破坏及反应性胶原的过度沉积,从而预防和逆转心室重构,改善心脏功能。AIM: To investigate the influence of fluv-astation on matrix metalloproteinase-2 ( MMP-2) and transforming growth factor beta-1 (TCF-β1) in the development of left ventricular remodeling and heart failure of rats after myocardial infarction (MI) and the mechanisms of left ventricular remodeling and heart failure after myocardial infarction. METHODS: 67 male Sprague-Dawley (SD) rats were randomly divided into three groups: the sham group, the MI group and the MI + statin group. The MI model was induced by ligating the left anterior descending coronary artery. After 24 hours of ligation, animals in the MI + statin group were treated with fluvastatin (4 mg·kg-1·d-1 ), and animals in the sham group and the MI group were treated with placebo. Rats were sacrificed 3 days, 4 weeks and 8 weeks after treatment. The content of MMP-2 protein (by Western-blot) and the expression of TGF-β1 were determined, and the collagen volume fraction (CVF) and the ratio of type Ⅰ to Ⅲ collagen (by immunohistochemistry) in the noninfarcted zone were assessed. Left ventricular function was measured atdifferent times. RESULTS: The levels of MMP-2 and TGF-β1 in the noninfarcted zone were significantly higher in the MI group and the MI + statin group than that in the sham group ( P < 0.05) , but it was significantly lower in the MI + statin group than that in the MI group ( P < 0.05) 3 days, 4 weeks and 8 weeks after treatment. Compared with the MI group, left ventricular function of rats in the MI + statin group was significantly improved. CVF and type Ⅰ /Ⅲ collagen ratio in the MI + statin group were significantly lower than that in the MI group ( P < 0.05) 4 weeks and 8 weeks after treatment. CONCLUSION: Fluvastatin can relieve the destruction of the collagen network and deposition of redundant reactive collagen in cardiac muscles through decreasing the MMP-2 and TGF-β1, of cardiac muscle in the noninfarcted zone. Fluvastatin can prevent and reverse the left ventricular remodeling and improve the cardiac function.

关 键 词：氟伐他汀 心衰 心室重构 基质金属蛋白 酶-2 转化生长因子-β1 

分 类 号：R972.6[医药卫生—药品]