β链蛋白在慢性缺氧诱导小鼠心肌肥厚中的作用

发布时间：2018-03-20 07:10

  本文选题：β链蛋白　切入点：紫绀型先天性心脏病　出处：《第三军医大学学报》2017年16期 　论文类型：期刊论文

【摘要】：目的探讨β链蛋白(β-catenin)在缺氧诱导的心肌肥厚中的作用,并寻找可能的干预靶点。方法 (1)收集第三军医大学新桥医院心外科2015年10月到2016年8月收治的21例先心病患儿的右室流出道临床心肌标本,常氧组(室间隔缺损伴右室流出道狭窄,血氧饱和度≥95%)10例和缺氧组(法洛氏四联征,血氧饱和度85%)11例,术中取右室流出道心肌组织作为标本,用免疫荧光检测心肌细胞面积,Western blot检测心肌胞质、胞核β-catenin含量。(2)选取25只成年C57小鼠,按照随机数字表法分为常氧4周组、缺氧4周组、缺氧4周+激动剂(CHIR-9901)组、缺氧4周+抑制剂(IWR-1)组和缺氧+生理盐水组(n=5)。常氧4周组和缺氧4周组于缺氧第4周取出心脏。小鼠缺氧模型采用10%氧浓度连续缺氧4周。通过免疫荧光标记细胞膜并测量心肌细胞面积,Western blot检测心肌中胞质和胞核的β-catenin及Cyclin D1的蛋白含量。(3)缺氧4周+激动剂组、缺氧4周+抑制剂组和缺氧4周+生理盐水组均在缺氧3周后,在缺氧舱内腹腔注射给药,第4周取得心脏。通过观察心室质量和心肌细胞面积比较心肌肥厚程度,小动物心导管检测心脏功能。结果 (1)临床标本中,相对于非紫绀组心肌,紫绀组的心肌面积明显增加(P0.05),且伴随着胞核、胞质中β-catenin的蛋白表达减少。(2)小鼠慢性缺氧模型中,缺氧4周组明显出现心肌细胞面积增加(P0.05),右心室与体质量的比值增加(P0.05),右心射血分数降低(P0.05),并伴随着胞核、胞质中β-catenin的蛋白表达减少。(3)与缺氧4周+生理盐水组比较,缺氧4周+激动剂组的心肌细胞面积减少(P0.05),右心室与体质量的比值减少(P0.05),右心射血分数增加(P0.05),胞核β-catenin水平和下游靶基因Cyclin D1表达水平明显增加,而缺氧4周+抑制剂组无明显变化(P0.05)。结论在慢性缺氧引起右心室肥厚过程中,β-catenin激活进入胞核,能减轻心肌肥厚,并改善心脏功能。
[Abstract]:Objective to investigate the beta chain protein (beta -catenin) in hypoxia induced myocardial hypertrophy in the role, and find out the possible target intervention. Methods (1) of 21 cases of children with congenital heart disease of Xinqiao Hospital Third Military Medical University from October 2015 to August 2016 were cardiac surgery of the right ventricular outflow tract clinical cardiac muscle samples, normoxia group (ventricular septal defect with right ventricular outflow tract stenosis, blood oxygen saturation is larger than 95%) and hypoxia group (10 cases of tetralogy of Fallot, oxygen saturation of 85%) in 11 cases, intraoperative from right ventricular outflow tract myocardium as samples, using the immunofluorescence detection of myocardial cell area, Western blot to detect myocardial cytoplasm, nucleus (beta -catenin content. 2) select 25 adult C57 mice were randomly divided into normoxic 4 weeks group, 4 weeks hypoxia group, hypoxia 4 weeks + agonist (CHIR-9901) group, hypoxia 4 weeks + inhibitor (IWR-1) group and hypoxia + saline group (n=5). 4 weeks normoxia group and hypoxia in the 4 week group Remove the heart. Fourth weeks hypoxia anoxia in mice model with 10% oxygen concentration in hypoxia for 4 weeks. By immunofluorescence labeling of cell membrane and measurement of myocardial cell area, protein content and beta -catenin Cyclin D1 cytoplasm and Western blot in the detection of myocardial nuclear. (3) 4 weeks hypoxia + agonist group, hypoxia 4 weeks + inhibitor group and hypoxia + saline group were 4 weeks in hypoxia after 3 weeks of hypoxia in the cabin after intraperitoneal injection, fourth weeks in heart. By observation of ventricular mass and cardiac myocyte area comparison of myocardial hypertrophy, cardiac function detection of small animal cardiac catheter. Results (1) clinical specimens, compared with non cyanosis group, cyanosis group myocardial area increased significantly (P0.05), and with the nucleus, -catenin expression in the cytoplasm of the protein decreased. (2) mice model of chronic hypoxia, hypoxia 4 weeks group appeared in the myocardial cell area increased significantly (P0.05), right ventricle and physique The increase of the ratio of (P0.05), right ventricular ejection fraction (P0.05) decreased, and accompanied by the nucleus, the expression of -catenin beta protein in cytoplasm decreased. (3) compared with 4 weeks of hypoxia + saline group, hypoxia 4 weeks + excited myocardial cell area agent group decreased (P0.05), the ratio of right ventricle and body weight reduction (P0.05), right ventricular ejection fraction (P0.05), nuclear beta -catenin level and downstream target gene Cyclin expression level of D1 increased significantly, while 4 weeks hypoxia + inhibitor group had no significant change (P0.05). Conclusion in chronic hypoxia induced right ventricular hypertrophy during beta -catenin activation into nucleus, can reduce myocardial hypertrophy and improve cardiac function.

【作者单位】： 乐山市人民医院胸心外科;第三军医大学新桥医院心血管外科;
【分类号】：R542.2
，

本文编号：1638022