机构地区:[1]中南大学湘雅医学院附属海口医院海口市人民医院心内科,海南海口570208
出 处:《中国医药导报》2020年第14期19-22,F0004,共5页China Medical Herald
基 金:海南省自然科学基金项目(20158339)。
摘 要:目的探讨小檗碱(BBR)对大鼠高血压左室肥厚心肌表达miRNA-29b的影响及抑制心肌纤维化的作用机制。方法将25只雄性SD大鼠随机分成假手术组(Sham组,n=7),模型组(Model组,n=9)和模型给药组(Model+BBR组,n=9)。腹主动脉缩窄法制备大鼠高血压心肌肥厚模型,术后8周测定各组超声心动图、心脏肥大指数,Masson染色检测心肌组织纤维化,RT-PCR检测心肌组织miRNA-29b及其靶基因col1α1和col3α1 mRNA表达。结果Model组的舒张末期室间隔厚度(IVSd)、舒张末期左室后壁厚度(LVPWd)均厚于Sham组,左室长轴缩短分数(FS)、射血分数(EF)均低于Sham组,差异有统计学意义(P<0.05);Model+BBR组的IVSd、LVPWd均薄于Model组,FS、EF均高于Model组,差异有统计学意义(P<0.05)。Model组的心脏重量显著重于Sham组,心脏/体重比显著高于Sham组(P<0.01);Model+BBR组的心脏重量轻于Model组,心脏/体重比低于Model组(P<0.05)。Model组的心肌胶原蛋白体积分数显著高于Sham组(P<0.01);Model+BBR组的心肌胶原蛋白体积分数低于Model组(P<0.05)。Model组的Col1α1 mRNA和Col3α1 mRNA水平均高于Sham组,miRNA-29b水平低于Sham组(P<0.05或P<0.01);Model+BBR组的Col1α1 mRNA和Col3α1 mRNA水平均低于Model组,miRNA-29b水平高于Model组(P<0.05)。结论BBR可能通过下调miRNA-29b水平及上调其靶基因表达水平,抑制高血压心肌肥厚模型心肌肥厚和心肌纤维化。Objective To investigate the effect of Berberine on expression of miRNA-29b in hypertensive left ventricular hypertrophy myocardial tissue and the mechanism of inhibition for myocardial fibrosis.Methods Male SD rats(n=25)were randomly divided into sham operation group(sham group,n=7),model group(model group,n=9)and model administration group(model+BBR group,n=9).Rat model of hypertensive cardiac hypertrophy was established by abdominal aortic coarctation.The cardiac structure and function were measured by echocardiography.The cardiac hypertrophy index was measured at 8 weeks postoperatively.The changes of myocardial fibrosis were detected by Masson staining.The expression of miRNA-29b and its target genes col1α1 and col3α1 mRNA in myocardial tissue were detected by RT-PCR.Results IVSd and LVPWd in model group were thicker than those in sham group,and FS and EF were lower than those in Sham group(P<0.05).IVSd and LVPWd of model+BBR group were thinner than those of model group,and FS and EF were higher than those of model group(P<0.05).Heart weight of model group was significantly heavier than that of sham group,and heart/body weight ratio was significantly higher than that of sham group(P<0.01).Heart weight of model+BBR group was lighter than that of model group,and the heart/body weight ratio was lower than that of model group(P<0.05).The volume fraction of myocardial collagen in model group was significantly higher than that in sham group(P<0.01).The volume fraction of myocardial collagen in model+BBR group was lower than that in model group(P<0.05).The level of col1α1 mRNA and col3α1 mRNA in model group was higher than those in sham group,and the level of miRNA-29b was lower than that in sham group(P<0.05 or P<0.01).The level of col1α1 mRNA and col3α1 mRNA in model+BBR group was lower than those in model group,and the level of miRNA-29b was higher than that in model group(P<0.05).Conclusion Berberine inhibits myocardial hypertrophy and myocardial fibrosis by down-regulating miRNA-29b levels and up-regulat
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