microRNA-33通过调节巨噬细胞自噬干预心肌细胞胆固醇代谢受损和功能缺陷

目的 探讨microRNA-33通过调节巨噬细胞自噬对心肌细胞胆固醇代谢受损和功能缺陷的影响.方法 分别培养人单核巨噬细胞和人心肌细胞后将实验分为对照组、miR-33模拟物组(10、5.0、1.0μmol/L组)和miR-33抑制剂组(10、5.0、1.0μmol/L组).分别测定各组巨噬细胞存活率和自噬相关蛋白表达水...

MicroRNA-33 interferes with impaired cholesterol metabolism and functional defects in cardiomyocytes by regulating macrophage autophagy

Objective To investigate the effect of microRNA-33 on impaired cholesterol metabolism and functional defects of myocardial cells by regulating macrophage autophagy.Methods Human mononuclear macrophages and human cardiomyocytes were cultured and divided into control group,microRNA-33 simulator group(10,5.0 and 1.0μmol/L)and microRNA-33 inhibitor group(10,5.0 and 1.0μmol/L).The macrophage survival rate and autophagy-related protein expression levels,the protein expression levels of myocardial cells ABCA1 and CS,cholesterol outflow rate,myocardial cell activity and functional defects[lactate dehydrogenase(LDH),superoxide dismutase(SOD),malondialdehyde(MAD)]were measured respectively in each group.Results There were significant differences in macrophage survival rate and autophagy-related protein expression levels,protein expression levels of cardiac muscle cells ABCA1 and CS,cholesterol outflow rate,cardiac muscle cell activity and functional defects(P<0.05).Among them,the macrophage survival rate in the mimic group showed higher protein expression and myocardial cell activity of ABCA1 and CS than those in the control group and the inhibitor group,cholesterol efflux rate was lower than the control group and the inhibitor group,and the functional defects was lower than the inhibitor group(P<0.05).As the concentration of microRNA-33 mimics increases,LC3-Ⅰ,LC3-Ⅱand ATG5,ABCA1 and CS protein expression levels,LDH and SOD levels increased significantly,while MAD levels decreased significantly(P<0.05).As the concentration of microRNA-33 inhibitor increases,Cardiomyocyte cholesterol outflow rate and MAD level increased significantly,LC3-Ⅰ,LC3-Ⅱand ATG5 protein expression levels,myocardial cell viability,and LDH and SOD levels were significantly reduced(P<0.05).Conclusion The mimic of microRNA-33 can increase the expression of macrophage autophagy protein,reduce the cholesterol metabolism level and the occurrence of functional defects in cardiomyocytes,and within the scope of this study,the higher the dose,the more significant the effect,while the regulatory effect of microRNA-33 mimics is opposite.