miR-320b激动剂对心肌梗死大鼠心室重塑的影响

Effect of miR-320b agonist on ventricular remodeling in rats with myocardial infarction

目的:探讨miR-320b激动剂对心肌梗死大鼠心室重塑的影响。方法:建立心肌梗死大鼠模型,将大鼠随机分为假手术组、模型组、阴性对照组、miR-320b过表达组。RT-PCR检测miR-320b、MHC-α、MHC-βmRNA水平;TTC染色检测心肌梗死面积;超声心动图检测左心室收缩压峰值(LVSP)、左心室舒张末期压(LVEDP)、左心室短轴缩短率(LVFS)和左心室射血分数(LVEF);H-E染色检测心肌组织形态学;TUNEL染色检测心肌细胞凋亡;免疫印迹检测凋亡相关蛋白表达水平;ELISA检测肿瘤坏死因子-α(TNF-α)、白细胞介素-1β(IL-1β)、白细胞介素-6(IL-6)水平。结果:与假手术组比较,模型组大鼠miR-320b、MHC-αmRNA水平降低,MHC-βmRNA水平和心肌梗死面积升高,LVEF、LVFS、LVSP降低,LVEDP升高,心肌组织细胞凋亡率升高,Bax/Bcl-2、cleaved caspase-3/caspase-3、cleaved caspase-9/caspase-9比值升高,TNF-α、IL-1β、IL-6水平升高,差异均有统计学意义。与模型组比较,miR-320b过表达组大鼠miR-320b、MHC-αmRNA水平升高,MHC-βmRNA水平和心肌梗死面积降低,LVEF、LVFS、LVSP升高,LVEDP降低,心肌组织病理损伤程度明显改善,心肌组织细胞凋亡率降低,Bax/Bcl-2、cleaved caspase-3/caspase-3、cleaved caspase-9/caspase-9比值降低,TNF-α、IL-1β、IL-6水平降低,差异均有统计学意义。结论:miR-320b过表达可改善心肌梗死大鼠模型心室重塑。

Objective:To investigate the effect of miR-320b agonist on ventricular remodeling in rats with myocardial infarction.Methods:Rat models of myocardial infarction were established and randomly divided into four groups:the sham operation group(sham),the model group(model),the negative control group(agomir-NC),and the miR-320b over-expression group(miR-320b agomir).The mRNA levels of miR-320b,MHC-αand MHC-βwere detected by RT-PCR.TTC staining was used to detect myocardial infarction area.Peak left ventricular systolic peak pressure(LVSP),left ventricular end-diastolic pressure(LVEDP),left ventricular fractional shortening rate(LVFS)and left ventricular ejection fraction(LVEF)were measured by echocardiography.H-E staining was used to detect myocardial histomorphology.Cardiomyocyte apoptosis was detected by TUNEL staining and expression of apoptosis-related proteins was detected by Western blotting.The levels of TNF-α,IL-1βand IL-6 were detected by ELISA.Results:Compared with the sham group,the mRNA levels of miR-320b and MHC-αin model group were decreased,while the mRNA levels of MHC-βand myocardial infarction area were increased,while LVEF,LVFS and LVSP were decreased,LVEDP was increased,and the apoptosis rate of myocardial tissue cells was increased.Ratio of Bax/Bcl-2,cleaved caspase-3/caspase-3,cleaved caspase-9/caspase-9,and TNF-α,IL-1βand IL-6 levels were increased with statistical significance.Compared with the model group,mRNA levels of miR-320b and MHC-αin miR-320b agomir group were increased,mRNA levels of MHC-βand myocardial infarction area were decreased,LVEF,LVFS,LVSP were increased,and LVEDAP was decreased.The degree of pathological injury of myocardial tissue was significantly improved.There were decreased apoptosis rate,decreased Bax/Bcl-2,cleaved caspase-3/caspase-3,cleaved caspase-9/caspase-9,decreased TNF-α,IL-1β,and IL-6 levels.The differences were statistically significant.Conclusion:Overexpression of miR-320b can improve ventricular remodeling in rats with myocardial infarction.