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目的探讨不同剂量卡维地洛治疗急性心肌梗死后大鼠心肌炎症因子和心肌基质金属蛋白酶表达与心功能的影响。方法结扎大鼠左冠状动脉前降支,建立急性心肌梗死(AMI)模型共48只,随机分为卡维地洛低剂量治疗组(CAR-L组,2.5 mg·kg~(-1)·d~(-1))、卡维地洛中剂量治疗组(CAR-M组,5.0 mg·kg~(-1)·d~(-1))、卡维地洛高剂量治疗组(CAR-H组,10.0 mg·kg~(-1)·d~(-1))和心肌梗死对照组(AMI组),每组12只;另设假结扎组(Sham组,12只)。连续灌胃治疗4周后,检测各组血浆炎症因子(IL-6、TNF-α、MIF)和心肌基质金属蛋白酶MMP-2、MMP-9水平以及超声心动图测试左室心功能。结果同Sham组比较,AMI组的组织促炎症因子IL-6、TNF-α、MIF和MMP-2、MMP-9含量明显增高(P<0.01),左室射血分数EF和FS%明显降低(P<0.01)。同AMI组比较,卡维地洛治疗组的IL-6、TNF-α、MIF和MMP-2、MMP-9含量明显降低(P<0.01),而且EF和FS%值明显增高(P<0.05),特别是CAR-M组和CAR-H组治疗效果更加明显。并且CAR-M组和CAR-H组的各项检测指标与Sham组无显著性差异(P>0.05)。结论中、高剂量卡维地洛不但可显著减少心肌梗死大鼠的促炎因子的表达,还能够明显降低心肌基质金属蛋白酶MMP-2和MMP-9的表达,从而抑制左心室重构,改善心功能。
Objective To investigate the effects of different doses of carvedilol on myocardial inflammatory cytokines and myocardial matrix metalloproteinase (MMP) expression and cardiac function after acute myocardial infarction in rats. Methods A total of 48 acute myocardial infarction (AMI) models were established and ligated into the anterior descending branch of left anterior descending coronary artery in rats. The rats were randomly divided into 2 groups: carvedilol low dose group (2.5 mg · kg -1) (CAR-M group, 5.0 mg · kg -1 · d -1), high-dose carvedilol treatment group (CAR- H group, 10.0 mg · kg -1 d -1) and myocardial infarction control group (AMI group), with 12 rats in each group. Sham group (n = 12) was also established. After continuous gavage for 4 weeks, the levels of inflammatory cytokines (IL-6, TNF-α, MIF) and MMP-2, MMP-9 in myocardium were measured and left ventricular function was measured by echocardiography. Results Compared with Sham group, the levels of IL-6, TNF-α, MIF and MMP-2, MMP-9 in AMI group were significantly increased (P <0.01) (P <0.01). The levels of IL-6, TNF-α, MIF, MMP-2 and MMP-9 in carvedilol group were significantly lower than those in AMI group (P <0.01) ), Especially the CAR-M group and CAR-H group more obvious treatment effect. There was no significant difference between the CAR-M group and the CAR-H group (P> 0.05). Conclusions Both medium and high doses of carvedilol can not only significantly reduce the expression of proinflammatory cytokines but also significantly decrease the expression of MMP-2 and MMP-9 in myocardial infarction rats and thus inhibit left ventricular remodeling and improve Cardiac Function.