摘要
目的:近来研究显示,心力衰竭是心室重塑的过程,其中基质金属蛋白酶2和9(MMP-2&9)作用最重要,本研究旨在使用美托洛尔干预异丙基肾上腺素(ISO)诱导SD大鼠充血性心力衰竭模型,观察心肌MMP-2&9变化并探讨其意义。方法:实验选用清洁级雄性SD大鼠60只,随机分为正常对照组(n=10)和模型组(n=50)。模型组大鼠皮下注射ISO 2次(170 mg.kg-1),6周后应用超声心动图检测,以左室射血分数≤45%确定造模成功。将心衰大鼠模型随机分为心衰对照组、美托洛尔组(8 mg.kg-1.d-1),18周使用左心导管进行血流动力学检查,取心肌检测心肌MMP-2&9的表达并观察病理形态学特征。结果:(1)与正常对照组相比,心衰对照组血流动力学指标明显恶化,心室质量指数、左心室质量指数和心肌MMP-2&9表达显著升高(P<0.01),心室重构明显;(2)与心衰对照组比较,美托洛尔组血流动力学指标明显好转,心室质量指数、左心室质量指数和心肌MMP-2&9表达明显降低(P<0.01),心室重构好转。结论:美托洛尔能抑制心力衰竭大鼠心肌MMP-2&9表达,改善心功能,逆转心室重构。
Objective： Recent studies have suggested that congestive heart failure（CHF） is a myocardial remode- ling and lead to the development and progression of CHF. And Matrix metalloproteinase 2 and 9 （MMPs-2 ＆ 9 ） were the most important factors. This study intends to establish the animal model of isoproterenol （ISO）- induced CHF in rats and to explore the effect of metoprolol on cardiac MMP-2 ＆ 9. Methods： 60 Male Sprague- Dawley rats were randomly allocated to the ISO-induced chronic heart failure group （n = 50） receiving two subcutaneous injec- tions of 170 mg ISO per-kilogram of body and the healthy normal group（n = 10） receiving two subcutaneous injec- tions of 0.25 ml normal saline. After 6 weeks, the left ventricular ejection fraction（LVEF） were measured by echo- cardiogram, the remaining rats, with an LVEF≤45%, were randomly divided into two groups： control group（ n =10）, metoprolol group 8 mg.kg-1·d-1 （n = 10）, the drugs were given i.g. At 18th week, then the hemodynamic parameters were detected, including heart rate, left ventricular end diastolic pressure, left ventricular systolic pres- sure; LVWI was measured after left ventricular morphopathological examination, the MMP-2 ＆ 9 in cardiac were detected by RT-PCR, real-time PCR and gelatin zymography assay method. Results： （1） Compared with the healthy normal group, the HR, LVEDP, VWI, LVWI and the MMP-2 ＆ 9 in cardiac were significantly increased （P 〈 0.01 ）, but LVSP and ± dp/dtmx were significantly decreased in the control group. （2） Compared with the control group, the HR, LVEDP, VWI, LVWI and the MMP-2 ＆ 9 in cardiac were decreased distinctly, the ± dp! dtm~, were increased distinctly（ P 〈0.01 ） in the metoprolol group. Conclusion： Metoprolol can inhibit the MMP- 2 ＆ 9 in cardiac, improve heart function and reverse ventricular remodeling with CHF.
出处
《现代医学》
2010年第1期19-23,共5页
Modern Medical Journal
基金
南京军区南京总医院科研基金资助项目(Q2008042)
