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

中国临床药理学与治疗学 ›› 2004, Vol. 9 ›› Issue (11): 1243-1247.

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

马静, 王虹, 哈黛文, 徐江¹

武汉大学中南医院综合医疗科,武汉大学医学院老年病研究所,¹生理系,武汉 430071,湖北

收稿日期:2004-08-24 修回日期:2004-09-24 出版日期:2004-11-26 发布日期:2020-11-19
通讯作者: 王虹,女,硕士生导师,主任医师,主要从事高血压冠心病研究。Tel: 027-67812612 E-mail: h〇]ig\vang9@yahoo.com.cn
作者简介:马静,女,硕士研究生。E-mail: jiaosilang@sina.com.cn

Influence of fluvastatin on MMP-2, TGF-β₁ and left ventricular remodeling in rats with heart failure

MA Jing, WANG Hong, HA Dai-Wen, XU Jiang¹

Department of Internal Medicine and Geriatrics, Zhongnan Hospital, Wuhan University; Institute of Geriatrics; ¹Department of Physiology, School of Medicine, Wuhan University, Wuhan 430071, Hubei, China

Received:2004-08-24 Revised:2004-09-24 Online:2004-11-26 Published:2020-11-19

摘要/Abstract

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、心梗组和心梗他丁组,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詞安慰剂。术后3 d、4周、8周检测大鼠非梗死区心肌MMP-2 的含量（Westem-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-的表达的变化趋势与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,股原容积分数(CVF)及 I/III 型脱原比值（Ratio of type I/HI)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-J3,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,从而子页防和逆转心室重构,改善心脏功能。

关键词: 氟伐他丁, 心衰, 心室重构, 基质金属蛋白酶-2, 转化生长因子-β₁

Abstract: AIM: To investigate the influence of fluv-astation on matrix metalloproteinase-2 (MMP-2) and transforming growth factor beta-1 (TGF-β₁) in the devel-opment of left ventricular remodeling and. heart failure of rats after myocardial infarction (MI) and the mechaiiisms of left ventricular remodeling and heart failure after myo-cardial infarction. METHODS: 67 male Spragiie-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 de-scending coronary artery. After 24 hours of ligation, ani-mals 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 sacri-ficed 3 days, 4 weeks and 8 weeks after treatment. The content of MMP-2 protein (by Western-blot) and the ex-pression of TGF-β₁ were detemiined, and the collagen vol-ume fraction (CVF) and the ratio of type I to HI colla-gen (by immunohistochemistry) in the noninfarcted zone were assessed. Left ventricular function was measured at different times. RESULTS: Tlie levels of MMP-2 and TGF-pj 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/IE 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 destmction of the col-lagen network and deposition of redundant reactive colla-gen in cardiac muscles through decreasing the MMP-2 and TGF-β₁ of cardiac muscle in the noninfarcted zone. Fluv-astatin can prevent and reverse the left ventricular remod-eling and improve the cardiac function.

Key words: fluvastatin, heart failure, ventriculai remodeling, MMP-2, TGF-β₁

中图分类号:

R972.6

马静, 王虹, 哈黛文, 徐江. 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[J]. 中国临床药理学与治疗学, 2004, 9(11): 1243-1247.

MA Jing, WANG Hong, HA Dai-Wen, XU Jiang. Influence of fluvastatin on MMP-2, TGF-β₁ and left ventricular remodeling in rats with heart failure[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2004, 9(11): 1243-1247.

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