CAJ | 학술논문

目的：探讨 microRNA-133（miR-133）在扩张型心肌病（DCM）心肌纤维化过程中的作用。方法收集行心脏移植的 DCM 患者心肌组织标本21例（DCM 组），意外创伤性脑死亡而无心脏疾病患者心肌组织标本10例（对照组）。Masson 染色观察心肌纤维化状况，原位末端标记法（TUNEL 法）观察心肌细胞凋亡情况。培养人心肌成纤维细胞，转染 miR-133模拟物（miR-133a mimic、miR-133b mimic），上调心肌成纤维细胞 miR-133（miR-133a、miR-133b）的表达，应用 RT-PCR 法检测 miR-133a、miR-133b 的表达，应用 RT-PCR、Western boltting 法分别检测BCL-2 mRNA 和蛋白水平表达。结果DCM 组心肌组织中出现严重的心肌纤维化和心肌细胞凋亡，左、右心室心肌间质和血管周围胶原（CVF）增多（P ＜0．01）；凋亡指数增高（P ＜0．05）；细胞凋亡相关蛋白 BCL-2表达上调（P ＜0．05）；人心肌成纤维细胞转染 miR-133a mimic、miR-133b mimic 后，miR-133a、miR-133b 表达上调（P ＜0．01），BCL-2表达显著下降（P ＜0．01）。结论DCM 心肌组织中 miR-133能够减弱 BCL-2对心肌成纤维细胞的诱导，抑制心肌成纤维细胞病理增生，减轻 DCM 心肌纤维化。
목적：탐토 microRNA-133（miR-133）재확장형심기병（DCM）심기섬유화과정중적작용。방법수집행심장이식적 DCM 환자심기조직표본21례（DCM 조），의외창상성뇌사망이무심장질병환자심기조직표본10례（대조조）。Masson 염색관찰심기섬유화상황，원위말단표기법（TUNEL 법）관찰심기세포조망정황。배양인심기성섬유세포，전염 miR-133모의물（miR-133a mimic、miR-133b mimic），상조심기성섬유세포 miR-133（miR-133a、miR-133b）적표체，응용 RT-PCR 법검측 miR-133a、miR-133b 적표체，응용 RT-PCR、Western boltting 법분별검측BCL-2 mRNA 화단백수평표체。결과DCM 조심기조직중출현엄중적심기섬유화화심기세포조망，좌、우심실심기간질화혈관주위효원（CVF）증다（P ＜0．01）；조망지수증고（P ＜0．05）；세포조망상관단백 BCL-2표체상조（P ＜0．05）；인심기성섬유세포전염 miR-133a mimic、miR-133b mimic 후，miR-133a、miR-133b 표체상조（P ＜0．01），BCL-2표체현저하강（P ＜0．01）。결론DCM 심기조직중 miR-133능구감약 BCL-2대심기성섬유세포적유도，억제심기성섬유세포병리증생，감경 DCM 심기섬유화。
Objective To investigate the effects of microRNA-133(miR-133)on myocardial fibrosis of dilated cardio-myopathy (DCM).Methods A total of 21 myocardial samples of DCM patients undergoing cardiac transplantation (DCM group)and 10 myocardial samples of brain-dead victims of accidental trauma who had no medical evidence of cardiac disease (control group)were collected.The degrees of myocardial fibrosis were observed with masson staining, and cardiomyocyte apoptosis was determined with TdT-mediated dUTP Nick-End Labeling (TUNEL).Human cardiac fibroblasts were cultured,and miR-133mimic(miR-133a mimic and miR-133b mimic)was transfected into the fibro-blasts to investigate the effects of miR-133(miR-133a and miR-133b)on myocardial fibrosis.The mRNA expressions of BCL-2 and miR-133 were detected with RT-PCR,and the protein expression of BCL-2 was evaluated with Western blotting.Results In DCM group,severe myocardial fibrosis and myocardial cell apoptosis were observed,collagen volume fraction (CVF)was increased (left ventricle P <0.01;right ventricle P <0.01),myocardial apoptosis index was higher (left ventricle P <0.05;right ventricle P <0.05 ),and apoptosis-related protein BCL-2 was increased (P <0.05;right ventricle P <0.05).After miR-133a mimic and miR-133b mimic were transfected into human cardiacfibroblasts,the expression of miR-133a and miR-133b were elevated (P <0.01)and BCL-2 was decreased (P <0.01). Conclusion In myocardial tissues of DCM patients,miR-133 can attenuate the stimulation on cardiac fibroblasts induced by BCL-2,inhibit pathologic proliferation of myocardial fibroblasts,and reduce myocardial fibrosis of DCM.