卡维地洛对急性心肌梗死后大鼠心室重塑及MMP/TIMP表达的影响

Effect of carvedilol on preventing from ventricular remodeling and expression of MMP-8/TIMP-1 in rats after acute myocardial infarction

关键词:  心肌梗死  心室重塑  基质金属蛋白酶  基质金属蛋白酶抑制剂  卡维地洛

Key words:  myocardial infarction  ventricle remodeling  matrix metalloproteinase  tissue inhibitor of metalloproteinase  carvedilol

摘要:

［目的］研究卡维地洛对大鼠心肌梗死后心室重塑及MMP/TIMP表达的影响。［方法］结扎大鼠左冠状动脉建立急性心肌梗死（AMI）模型, 术后24 h存活大鼠随机分为心肌梗死对照组（MI 组），卡维地洛干预组（C组），另设假手术组（S 组）对照。C组给予卡维地洛［10 mg/ （kg·d）］分两次直接灌胃，MI 组和S 组大鼠则予等量蒸馏水。4周后检测各组血流动力学、心室重塑指标。采用免疫组化法检测心室肌中MMP-8和TIMP-1的表达。［结果］与假手术组相比，MI组的左室舒张末压（LVEDP）、容积（LVV）、重量（LVW）明显增加，分别为（2.2±2.0）mmHg和（19.9±12.8）mmHg，（0.43±0.11）mL和（0.91±0.08）mL，（525±62）mg和（714±64）mg，P＜0.01，MMP-8和TIMP-1表达明显增加（分别为35.5±0.27和97.6±0.21，43.6±0.24和89.5±0.21，P＜0.01），而心率及各项心功能指标如左心室收缩压（LVESP）和左心室内压最大上升和下降速率（±dp/dt）及其校正值（±dp/dt/LVSP）明显降低（P＜0.05～0.01）；与MI组相比，C组在卡维地洛治疗4周后LVEDP、LVV、LVW、明显降低，分别为（19.9±12.8）mmHg和（11.9±9.8）mmHg ，P＜0.01，（0.91±0.08）mL和（0.73±0.10）mL，P＜0.05，（714±64）mg和（623±59）mg，P＜0.01，MMP-8和TIMP-1表达亦均明显降低（分别为70.4±0.24和97.6±0.21，76.3±0.18和89.5±0.21，P＜0.01），而LVESP、±dp/dt、±dp/dt/LVSP明显升高（P＜0.05～0.01）。［结论］①卡维地洛能有效抑制AMI后大鼠心室重塑并改善血流动力学和左室功能。②卡维地洛有可能通过影响MMP/TIMP表达平衡从而改善AMI后大鼠心室重塑。

Abstract:

［Objective］To investigate the effect of carvedilol on Preventing from Ventricular Remodeling and expression of cardiac matrix metalloproteinases(MMPs) and tissue inhibitor of metalloproteinase(TIMPs) after myocardial infarction in rats.［Methods］Rat models with acute myocardial infarction were established by the ligation of left anterior descending coronary.Twenty-four hours after the operation, Rats were randomly divided into sham-operated group (group S) ,acute myocardial infarction group (group MI) and carvedilol group (group C) . Carvedilol group were treated with carvedilol ［10mg/(kg·d)］by gastric gavage,the other two groups were treated with the same amount of distillded water.After 4 weeks of therapy, hemodynamic studies were performed. The heart of rat was fixed and analyzed pathologically.The protein expressions of MMP-8 and TIMP-1 were examined by immunohistochemical analysis.［Results］Compared with sham-operated group, left ventricular (LV) end diastolic pressure (LVEDP) , volume(LVV) and weight(LVW) were all significantly increased ［(19.9±12.8)mmHg vs(2.2±2.0)mmHg,(0.43±0.11)mL vs (0.91±0.08)mL,(525±62)mg vs(714±64)mg,P<0.01］; while maximal rate of rise and fall (+ dp /dt) of LV pressure as well as their corrected values(+ dp /dt /LVSP) were significantly reduced (P<0.05～0.01) at 4 weeks after AMI, indicating decreased LV function and ventricular remodeling.while the protein expression of MMP-8, TIMP-1 were significantly increased (35.5±0.27 vs 97.6±0.21,43.6±0.24 vs 89.5±0.21,P<0.01),After four week carvedilol treatment, the LVEDP,LVV and LVW were significantly reduced ［(19.9±12.8)mmHg vs(11.9±9.8)mmHg,P<0.01,(0.91±0.08)mL vs (0.73±0.10)mL,P<0.05,(714±64)mg vs(623±59)mg,P<0.01］,while the protein expression of MMP-8 and TIMP-1 were significantly reduced by 27.9%, 14.8%( 70.4±0.24 vs 97.6±0.21,76.3±0.18 vs 89.5±0.21,P<0.01), whereas + dp /dt , + dp /dt /LVSP were significantly increased (P<0.05～0.01) at 4 weeks after AMI.［Conclusion］① Carvedilol can effectively attenuate ventricular remodeling and improve hemodynamics and LV function after AMI in rats. ② Carvedilol may effect the balance of MMP-8/TIMP-1 in Rats After AMI. It is one of causes of alleviating ventricular remodeling.