普伐他汀与阿托伐他汀对大鼠心梗后胞外基质重构及基质金属蛋白酶的影响

目的探讨他汀类药物对大鼠心肌梗死(MI)后胞外基质重构的作用机制,以及普伐他汀与阿托伐他汀对基质金属蛋白酶-2(MMP-2)和心室重构的影响。方法将雄性大鼠50只随机分为MI组、MI 普伐他汀组、MI 阿托伐他汀组和伪手术组。结扎冠状动脉前降支建立心肌梗死(MI)模型,在相应部位挂线不结扎作为伪手术组。8周后血流动力学检查,测量体质量(BW)、左、右心室质量(LVW,RVW);苦味酸-酸性品红染色检测非梗死区的胶原容积分数(CVF),ELISA法检测血清基质金属蛋白酶2(MMP-2)水平。结果MI组RVW/BW,LVW/BW,左室舒张末压(LVEDP)、非梗死区CVF均显著升高,MMP-2的水平亦明显升高(P均<0.05);与MI组比较,MI 他汀组的RVW/BW,LVW/BW,LVEDP,CVF显著降低,血清MMP-2水平显著减弱(P均<0.05)。两用药组间上述指标差异均无显著性(P>0.05)。结论他汀类药物缓解了MI后心肌细胞外基质的重构,其机制可能与基质金属蛋白酶(MMPs)的表达和活性调节有关。而普伐他汀与阿托伐他汀两组药物在心肌重构中差异无显著性。

The effect of pravastatin and atorvastatin on extracellular matrix remodeling and matrix metalloproteinase after myocardial infarction in rats

Objective To investigate the statins' effect on myocardial extracellular matrix remodeling after myocardial infarction (MI) in rats,and pravastatin and atorvastatin influenced matrix metalloproteinase 2 (MMP-2) expression and ventricular remodeling.Methods Fifty rats were randomized into 4 groups:MI group,MI pravastatin group,MI atorvastatin group and sham-operation group.The models of MI were induced by ligated with anterior descending coronary artery;the sham-operation group was made by the same procedure without ligation.The rats were killed 8 weeks after operation to examine hemodynamic parameters,body weight (BW),left and right ventricular weight (LVW,RVW).Collagen volume fraction (CVF)was measured by using Van Gieson(VG) in noninfarcted region; the expressions of MMP-2 were detected with ELISA.Results The RVW/BW,LVW/BW,left ventricular end-diastolic pressure (LVEDP) and CVF increased significantly,and the level of MMP-2 were enhanced in MI group (P<0.05).Compared with the MI group,RVW/BW,LVW/BW,LVEDP and CVF decreased significantly and the level of MMP-2 were weakened in the MI statins group (P<0.05).But there was no significant difference between the statins treated groups (P>0.05).Conclusion Statins can prevent myocardial extracellular matrix remodeling,which is associated with the MMP-2 expressions and activities.There were no significant differences in preventing myocardial extraceltular matrix remodeling between pravastatin and atorvastatin groups.