微小RNA-762表达与大鼠受损心脏中线粒体功能和心脏功能的关系研究

Relationship among microRNA-762 expression, mitochondrial function and heart function in rats with injured heart

目的 探讨微小RNA-762(miRNA-762)表达与大鼠受损心脏中线粒体功能和心脏功能的关系。方法 30只SD大鼠分为A组、B组、C组三组,每组各10只,B组和C组采用结扎左冠状动脉(冠脉)前降支法制备心肌缺血再灌注损伤模型,A组将前室间支分离但不结扎。造模成功后,C组给予50μl miRNA-762 antagomir尾静脉注射,B组和A组给予等量生理盐水尾静脉注射。造模成功后的第14 d,比较各组大鼠心肌梗死面积、心肌细胞凋亡率、心脏线粒体功能[线粒体膜电位、线粒体过氧化物生成量、线粒体三磷酸腺苷(ATP)生成量]、心脏功能[左室收缩末期内径(LVEDs)、左室射血分数(LVEF)、左室短轴缩短率(LVFS)、左室舒张末期内径(LVEDd)]、心肌组织中mi RNA-762表达量。结果 C组和B组大鼠心肌梗死面积、心肌细胞凋亡率、心脏线粒体过氧化物生成量、LVEDd、LVEDs、miRNA-762表达量显著高于A组(P<0.05);C组大鼠心肌梗死面积、心肌细胞凋亡率、心脏线粒体过氧化物生成量、LVEDd、LVEDs、mi RNA-762表达量显著低于B组(P<0.05);C组和B组大鼠心脏线粒体ATP生成量、线粒体膜电位、LVEF、LVFS显著低于A组(P<0.05);C组大鼠心脏线粒体ATP生成量、线粒体膜电位、LVEF、LVFS显著高于B组(P<0.05)。结论 抑制微小RNA-762表达能够促进大鼠受损心脏中线粒体功能和心脏功能恢复,这可为心脏疾病及线粒体相关疾病的治疗提供新的策略。

Objective To discuss the relationship among microRNA-762(miRNA-762) expression,mitochondrial function and heart function in rats with injured heart. Methods SD rats(n=30) were divided into group A, group B, group C and group D(each n=10). The model of myocardial ischemia reperfusion injury(MIRI) was established through ligating left anterior descending coronary artery in groups B and C, and anterior interventricular branch was separated only without ligation in group A. After model established successfully, group C was given caudal vein injection of miRNA-762 antagomir(50 μl), and groups B and A were given caudal vein injection of same amount of normal saline. After model established successfully for 14 d, various indexes were compare among all groups,including myocardial infarction area, apoptosis rate of myocardial cells, cardiac mitochondrial function [mitochondrial membrane potential(MMP), produced quantity of mitochondrial peroxide, produced quantity of mitochondrial adenosine triphosphate(ATP)], heart function indexes [left ventricular end-systolic diameter(LVESd), left ventricular ejection fraction(LVEF), left ventricular fraction shortening(LVFS), left ventricular end-diastolic inner diameter(LVEDd)], and expression of myocardial miRNA-762. Results The indexes of myocardial infarction area, apoptosis rate of myocardial cells, produced quantity of mitochondrial peroxide, LVEDd, LVEDs and miRNA-762 expression were significantly higher in groups C and B than those in group A(P<0.05). The indexes of myocardial infarction area,apoptosis rate of myocardial cells, produced quantity of mitochondrial peroxide, LVEDd, LVEDs and miRNA-762expression were significantly lower in group C than those in group B(P<0.05). The produced quantity of ATP, MMP,LVEF and LVFS were significantly lower in groups C and B than those in group A(P<0.05). The produced quantity of ATP, MMP, LVEF and LVFS were significantly higher in group C than those in group B(P<0.05). Conclusion The inhibition of RNA-762 expression can improve mitochondrial function and heart function recovery in rats with injured heart, which can provide new strategies for the treatment of heart diseases and mitochondrial-related diseases.