摘要
目的 :探讨微小核糖核酸-34a(miRNA-34a)对左心室肥厚大鼠心肌组织肌球蛋白重链α基因表达的调控及其意义。方法 :将40只雄性SD大鼠随机分为4组(n=10),分别为腹主动脉缩窄术后皮下注射miRNA-34a表达阻遏物组(ant-34a/AAC组),腹主动脉缩窄术后皮下注射miRNA-34a表达阻遏物阴性对照物组(con/AAC组),假手术后皮下注射miRNA-34a表达阻遏物组(ant-34a/SH组),假手术后皮下注射miRNA-34a表达阻遏物阴性对照物组(con/SH组)。模型建立第12周存活大鼠:ant-34a/AAC组6只,con/AAC组7只,ant-34a/SH组8只,con/SH组8只。测定各组大鼠左心室收缩压、左心室舒张末期压及压力最大变化速率,计算心肌肥厚指数,观察心肌组织病理学改变,应用荧光定量逆转录-聚合酶链反应(qRT-PCR)检测大鼠左心室心肌组织miRNA-34a、肌球蛋白重链α基因表达水平。结果:与con/AAC组相比,ant-34a/AAC组心肌肥厚指数、左心室收缩压、左心室舒张末期压以及miRNA-34a相对表达量降低,压力最大变化速率、肌球蛋白重链α基因相对表达量明显升高(P均<0.05)。与con/AAC组相比,con/SH组心肌肥厚指数、左心室收缩压、左心室舒张末期压以及miRNA-34a相对表达量明显降低,压力最大变化速率、肌球蛋白重链α基因相对表达量明显升高(P均<0.05)。与con/SH组相比,ant-34a/SH组miRNA-34a相对表达量明显降低,肌球蛋白重链α基因相对表达量明显升高(P均<0.05),心肌肥厚指数、左心室收缩压、左心室舒张末期压、压力最大变化速率差异无统计学意义(P>0.05)。结论:压力负荷性左心室肥厚大鼠心肌组织中miRNA-34a表达上调,肌球蛋白重链α基因表达减少,利用特异性阻遏物阻断miRNA-34a表达可使大鼠肥厚心肌组织肌球蛋白重链α基因表达水平增高,减轻或者延缓心肌肥厚、提高心肌顺应性、改善心功能。
Objective： To explore the regulation effect of microRNA-34a （miR-34a） on myosin heavy chain α （α-MHC） expression in rats of left ventricular hypertrophic tissue with overloaded pressure. Methods： The cardiac hypertrophy rats＇ model was established by abdominal aortic constriction （AAC）, and 40 SD rats were randomly divided into 4 groups. ① AAC rats with LNA-anti-miR-34a （ant-34a/AAC） group, ② AAC rats with LNA-control-34a （con/AAC） group, and ③ sham operation rats with LNA-anti-miR-34a （ant-34a/SH） group, ④ con/ SH group, n=10 in each group. With 12 weeks treatment, the surviving conditions were as 6 in ant-34a/AAC group, 7 in con/AAC group, and 8 in ant-34a/SH group, 8 in con/SH group. The left ventricular systolic pressure （LVSP）, left ventricular eud distolic pressure （LVEDP）, the maximum changing rate of pressure （±LVdp/dt）max, heart weight index （HM/ BM） and cardiac index （LVM/BM） were calculated, the pathological changes of myocardial tissue was observed and the expressions of miR-34a and α-MHC in the left ventricular tissue were analyzed. Results： Compared with con/AAC group, the ant-34a/AAC group had decreased HM/BM, LVSP, LVEDP and miR-34a expression, increased （±LLVdp/dt）max and α-MHC expression, all P〈0.05. Compared with con/AAC group, the con/SH group showed decreased HM/BM, LVSP, LVEDP and rniR-34a expression, increased （±LVdp/dt）max and et-MHC expression, all P〈0.05. Compared with con/SH group, the ant-34a/SH group presented decreased miR-34a expression and increased a-MHC expression, both P〈0.05; the HM/BM, LVSP, LVEDP and （±LVdp/dt）max were similar, all P〉0.05. Conclusion： The rats of left ventricular hypertrophy with overloaded pressure had increased miR-34a and decreased α-MHC, LNA-anti-miR-34a could elevate α-MHC expression and therefore, reduce or delay the myocardial hypertrophy and improve the cardiac function.
出处
《中国循环杂志》
CSCD
北大核心
2014年第2期138-141,共4页
Chinese Circulation Journal
基金
河南省科技厅科研基金(72102310023)
