【摘要】 目的:探讨不同β受体阻滞剂对心肌梗死(心梗)大鼠模型心肌胶原重构的影响。方法:取SD雄性大鼠,采用结扎前降支方法建立慢性心梗模型,将存活大鼠随机分组为心梗组(n=9)、卡维地洛组(n=10)、美托洛尔组(n=8)。并建立假手术模型假手术组(n=10),行心肌纤维化指标测定、基质金属蛋白酶(MMPs)活性测定及基质金属蛋白酶-13(MMP-13)及基质金属蛋白酶组织抑制剂-1(TIMP-1)的mRNA表达。结果:心梗组羟脯氨酸水平明显高于假手术组及卡维地洛组(P均<0.05),而在卡维地洛组则明显低于美托洛尔组(P<0.05);同假手术组相比,心肌梗死后MMP-2、MMP-9酶活性增加,进行药物干预后卡维地洛组MMP-2、MMP-9活性较心梗组显著下降(P<0.05);心梗组、美托洛尔组与假手术组相比较MMP-13的mRNA表达显著增高,差异有统计学意义(P均<0.05),经药物干预后卡维地洛组与美托洛尔组、心梗组比较显著下降,差异有统计学意义(P均<0.05)。心梗组、美托洛尔组与假手术组比TIMP-1的mRNA表达显著降低,差异有统计学意义(P均<0.05),与卡维地洛组比较亦显著降低,差异有统计学意义(P<0.05)。结论:卡维地络较美托洛尔有更强抑制心梗后心肌纤维化的作用,而这种作用可能同MMPs、TIMPs活性及mRNA表达有关。更多还原

【Abstract】 Objective:To study the effects of different β-adrenergic receptor blockers on cardiac fibrosis during heart failure after myocardial infarction in rats.Methods:Animals used in this study were male Sprague-Dawley rats.The left coronary artery was ligated near its origin to estabilish the heart failure model.The rats were randomly divided into 4 groups after four weeks:carvidilol group(n=10),sham group(n=10),metoprolol group(n=8)and heart failure group(n=9).Twelve weeks later,concentration of hydroxyproline was analysed.The mRNA expressions of MMP-13/TIMP-1 were measured by RT-PCR.Results:Concentration of hydroxyproline in heart failure group was significantly higher than that in carvidilol and sham group(P<0.05),carvedilol group has lower concentration of hydroxyproline compared with metoprolol group(P<0.05).Activity of MMP-2 and MMP-9 in heart failure group were higher than that in sham group and markedly downregulated in carvedilol group compared to that in metoprolol group.The expression of MMP-13 mRNA in metoprolol group(2.08±0.85) was significantly higher than that in carvedilol group(0.75±0.45,P<0.05),and also significantly higher than that in sham group(0.62±0.15,P<0.05).conversely,the mRNA expression of TIMP-1 in carvedilol group(1.89±0.65) was significantly increased compared to that in metoprolol group(1.45±0.87,P<0.05).Conclusion:Compared with metoprolol,carvedilol could decrease the concentration of hydroxyproline,suggesting that carvedilol could inhibit cardiac fibrosis during heart failure after myocardial infaction in rats.The underlying mechanism was supposed to be related to the altered activity and mRNA expression of MMPs/TIMPs.MMPs/TIMPs and the mRNA experssions of MMP-13/TIMP-1.更多还原