摘要
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。
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.
出处
《广东药学院学报》
CAS
2007年第6期673-675,678,共4页
Academic Journal of Guangdong College of Pharmacy
