依那普利对压力超负荷诱导的心肌纤维化的影响及microRNA-214的表达变化

【摘要】 目的探讨压力超负荷导致心肌纤维化过程中microRNA-214的表达变化,以及依那普利对心肌纤维化的影响。方法 80只雄性SD大鼠随机分为压力超负荷组(Model,n=40),假手术组(Sham,n=40)。其中各组再随机分为两个亚组:依那普利治疗组(n=20)与无依那普利治疗组(n=20)。行腹主动脉缩窄术建立心脏压力超负荷大鼠模型。4周后,酶联免疫分析法测定各组大鼠血清中的PICP、ICTP、MMP-2、TIMP-2等心肌纤维化指标,荧光实时定量PCR技术检测的microRNA-214表达变化。结果压力超负荷组大鼠的PICP为(161.3±16.3)ng/L、ICTP为(3.06±0.5)、PICP/ICTP比值为(51.1±7.3)、MMP-2为(2638.2±289.6)pg/mL、TIMP-2为(4396±365.9)ng/mL,上述指标与假手术相比,均有所增高,差异具有统计学意义(P均<0.05);模型组MMP-2/TIMP-2比值为(0.6±0.4),显著低于假手术组(P<0.05),依那普利处理亚组的大鼠PICP为(114.1±19.6)ng/L、ICTP为(2.5±0.7)ng/L、PICP/ICTP比值为(45.1±16.3)、MMP-2为(806.8±301.6)pg/mL、TIMP-2为(2052.6±322.3),均低于单纯压力超负荷组,异具有统计学意义(P均<0.05)。依那普利处理亚组MMP-2/TIMP-2比值为(0.88±0.3),显著高于单纯压力超负荷组,差异具有统计学意义(P均<0.05)。同时压力超负荷处理会导致microRNA-214的表达相对于假手术组增高(2.1±0.3)倍,依那普利处理可以缓解压力超负荷引起的microRNA-21过表达,但仍为假手术组的(1.5±0.2)倍。结论依那普利可以缓解压力超负荷造成的心肌纤维化,microRNA-214与此过程有关,可作为心肌纤维化的治疗靶点或标志物。更多还原

【Abstract】 Objective To investigate the expression of microRNA-214 in the myocardial fibrosis induced by pressure-overloaded treatment and the effect of enalapril in this process. Methods 80 male Spargue Dawley rats randomly was divided two groups: sham-operation group(n=40) and pressure-overloaded group(n=40),each group was divided two subgroups: enalapril treatment subgroup(n=20) and without enalapril treatment subgroup(n=20). Using ELISA kits to detect the level of PICP, ICTP, MMP-2 and TIMP-2 in serum, furthermore qrt-PCR was used to analyzed the expression of microRNA-214. Results Compared with the sham group pressure-overloaded treatment can increase the level of PICP, ICTP, PICP/ICTP ratio, MMP-2 and TIMP-2 significantly[(161.3±16.3) ng/L,(3.06±0.5),(51.1±7.3),(2638.2±289.6)pg/mL,(4396±365.9)ng/mL, P<0.05], after enalapril treatment the level of PICP, ICTP, PICP/ICTP ratio, MMP-2 and TIMP-2 were decreased[(2.5±0.7)ng/L,(45.1±16.3),(806.8±301.6) pg/mL,(2052.6±322.3),P<0.05]. MPP-2/ TIMP-2 ratio was(0.6±0.4) that is the lowest in pressure-overloaded group, After enalapril treatmen, MPP-2/ TIMP-2 ratio was elevated to(0.88±0.3). Meanwhile pressure-overloaded treatment can induce microRNA-214 overexpression[(2.1±0.3) fold relative to Sham group] and enalapril can decreased the expression of microRNA-214[(1.5±0.2) fold relative to Sham group]. Conclusion Enalapril can relieve the myocardial fibrosis caused by pressure-overloaded treatment and microRNA-214, which may be a target or indicator for therapy of myocardial fibrosis, was involved in this process.更多还原