CAJ | 학술논문

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。
목적：탐토압력초부하도치심기섬유화과정중microRNA-214적표체변화，이급의나보리대심기섬유화적영향。방법80지웅성SD대서수궤분위압력초부하조（Model，n=40），가수술조（Sham，n=40）。기중각조재수궤분위량개아조：의나보리치료조（n=20）여무의나보리치료조（n=20）。행복주동맥축착술건립심장압력초부하대서모형。4주후，매련면역분석법측정각조대서혈청중적PICP、ICTP、MMP-2、TIMP-2등심기섬유화지표，형광실시정량PCR기술검측적microRNA-214표체변화。결과압력초부하조대서적PICP위(161.3±16.3)ng/L、ICTP위(3.06±0.5)、PICP/ICTP 비치위(51.1±7.3)、MMP-2위(2638.2±289.6)pg/mL、TIMP-2위(4396±365.9)ng/mL，상술지표여가수술상비，균유소증고，차이구유통계학의의(P균<0.05)；모형조MMP-2/TIMP-2비치위(0.6±0.4)，현저저우가수술조（P<0.05），의나보리처리아조적대서PICP위(114.1±19.6)ng/L、ICTP위(2.5±0.7)ng/L、PICP/ICTP비치위(45.1±16.3）、MMP-2위(806.8±301.6)pg/mL、TIMP-2위(2052.6±322.3)，균저우단순압력초부하조，이구유통계학의의（P균<0.05）。의나보리처리아조MMP-2/TIMP-2비치위(0.88±0.3)，현저고우단순압력초부하조，차이구유통계학의의(P균<0.05)。동시압력초부하처리회도치microRNA-214적표체상대우가수술조증고（2.1±0.3）배，의나보리처리가이완해압력초부하인기적microRNA-21과표체，단잉위가수술조적（1.5±0.2）배。결론의나보리가이완해압력초부하조성적심기섬유화，microRNA-214여차과정유관，가작위심기섬유화적치료파점혹표지물。
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.