miRNA-1对慢性充血性心力衰竭小鼠左心室心肌Cx43蛋白表达的影响  

Effect of miRNA-1 on the expression of Cx43 protein in left ventricular myocytes of the mice with chronic congestive heart failure

作　　者：唐诗倩 陆士娟[1] 马添翼[1] 吴淼[1] 黄康[1] 张伟 钟江华[1] TANG Shiqian;LU Shijuan;MA Tianyi;WU Miao;HUANG Kang;ZHANG Wei;ZHONG Jianghua(Department of Cardiology,Haikou Hospital Affiliated to Xiangya School of Medicine,Central South University,Haikou 570000,China)

机构地区：[1]中南大学湘雅医学院附属海口医院心内科,海南海口570000

出　　处：《沈阳药科大学学报》2021年第7期706-713,共8页Journal of Shenyang Pharmaceutical University

基　　金：海南省自然科学基金(2018CXTD349)。

摘　　要：目的观察microRNA-1(miR-1)对慢性充血性心力衰竭(chronic heart failure, CHF)小鼠左心室心肌Cx43蛋白表达的影响。方法将24只小鼠随机分为假手术组(Sham组,n=8)、慢性充血性心力衰竭组(CHF组,n=8)和miR-1抑制剂组(CHF+antagomir组,n=8)。通过胸主动脉缩窄术构建CHF模型,Sham组开胸不结扎,以上同等条件下喂养8周。模型建立后,对Sham组和CHF组予以生理盐水,CHF+antagomir组建造CHF模型后予以antagomir,尾静脉注射,3天1次,连续2周,再行超声心动图检测各组小鼠左心室舒张末期内径(left ventricular end-diastolic diameter, LVEDD)、左心室收缩末期内径(left ventricular end-systolic diameter, LVESD)、左室射血分数(left ventricular ejection fraction, LVEF)以及左室短轴缩短率(fraction shortening, FS);酶联免疫法检测血清NT-proBNP水平;然后取小鼠左心室心脏组织行病理切片及Masson染色;RT-qPCR检测各组小鼠左心室心肌miRNA-1及Cx43 mRNA的表达;Western blotting检测各组小鼠左心室心肌Cx43蛋白表达。结果与Sham组对比,CHF组的心脏重量比(heart weight to body weight, HW/BW)、左心室重量比(left ventricle weight to heart weight, LVW/HW)明显上升,LVEF、FS明显降低,LVEDD、LVESD显著增加(P<0.05),而CHF+antagomir组和CHF组两组之间指标无明显差异(P>0.05);酶联免疫法检测结果显示,CHF+antagomir组小鼠血清NT-proBNP水平较CHF组明显下降(P<0.05),但仍高于Sham组(P<0.05);RT-qPCR检测结果显示,相较于Sham组,CHF组miR-1表达明显增加(P<0.05),Cx43 mRNA明显降低(P<0.05),CHF+antagomir组小鼠miR-1表达明显低于CHF组(P<0.05),Cx43 mRNA表达量则高于CHF组(P<0.05);Western blot结果显示,与Sham组对比,CHF组小鼠Cx43蛋白的表达明显下降(P<0.05),而CHF+antagomir组小鼠Cx43蛋白表达显著高于CHF组(P<0.05)。结论 CHF小鼠左心室心肌miR-1表达升高,而抑制miR-1可以改善Cx43蛋白的表达。Objective To observe the effect of microRNA-1(miR-1) on the expression of Cx43 protein in the left ventricular myocytes of the mice with chronic congestive heart failure(CHF).Methods 24 mice were randomly divided into 3 groups, i.e.,Sham-operated group(Sham, n=8),chronic congestive heart failure group(CHF group, n=8) and miR-1 inhibitor group(CHF+antagomir group, n=8).CHF mouse model was constructed by thoracic aorta ligation, and thoracotomy was performed in the Sham group without ligation.These mice were fed under the same conditions for 8 weeks.After the construction of CHF model, the mice in Sham group and CHF group were treated with normal saline, while the CHF + antagomir group was treated with antagomir after the establishment of the CHF model by tail vein injection every three days for 2 weeks.Subsequently, echocardiography was conducted to detect the left ventricular end-diastolic diameter(LVEDD),left ventricular end-systolic diameter(LVESD),left ventricular ejection fraction(LVEF) and fraction shortening(FS) of the mice in each group.Enzyme-linked immunosorbent assay for serum NT-proBNP levels.Then, the left ventricular cardiac tissues of the mice were taken for pathological section and Masson staining;RT-qPCR was performed to detect the expression of miRNA-1 and Cx43 mRNA in left ventricular myocytes of the mice in each group;meanwhile, Western Blotting was used to detect the expression of Cx43 in left ventricular myocardium of these mice.Results Compared with the Sham group, the ratio of heart weight to body weight(HW/BW) as well as the ratio of left ventricle weight(LVW) to heart weight(LVW/HW) of the CHF group were obviously increased, while LVEF and FS were significantly reduced, moreover, LVEDD and LVESD were remarkably elevated(P<0.05);however, there was no obvious distinct among the above parameters of CHF+antagomir group and CHF group(P>0.05);The results of enzyme-linked immunosorbent assay showed that serum NT-proBNP levels in CHF+antagomir group were significantly lower than those in CHF grou

关 键 词：心力衰竭 MICRORNA-1 CX43 治疗 

分 类 号：R96[医药卫生—药理学]