本文選題：β鏈蛋白　切入點(diǎn)：紫紺型先天性心臟病　出處：《第三軍醫(yī)大學(xué)學(xué)報(bào)》2017年16期 　論文類型：期刊論文

【摘要】：目的探討β鏈蛋白(β-catenin)在缺氧誘導(dǎo)的心肌肥厚中的作用,并尋找可能的干預(yù)靶點(diǎn)。方法 (1)收集第三軍醫(yī)大學(xué)新橋醫(yī)院心外科2015年10月到2016年8月收治的21例先心病患兒的右室流出道臨床心肌標(biāo)本,常氧組(室間隔缺損伴右室流出道狹窄,血氧飽和度≥95%)10例和缺氧組(法洛氏四聯(lián)征,血氧飽和度85%)11例,術(shù)中取右室流出道心肌組織作為標(biāo)本,用免疫熒光檢測(cè)心肌細(xì)胞面積,Western blot檢測(cè)心肌胞質(zhì)、胞核β-catenin含量。(2)選取25只成年C57小鼠,按照隨機(jī)數(shù)字表法分為常氧4周組、缺氧4周組、缺氧4周+激動(dòng)劑(CHIR-9901)組、缺氧4周+抑制劑(IWR-1)組和缺氧+生理鹽水組(n=5)。常氧4周組和缺氧4周組于缺氧第4周取出心臟。小鼠缺氧模型采用10%氧濃度連續(xù)缺氧4周。通過(guò)免疫熒光標(biāo)記細(xì)胞膜并測(cè)量心肌細(xì)胞面積,Western blot檢測(cè)心肌中胞質(zhì)和胞核的β-catenin及Cyclin D1的蛋白含量。(3)缺氧4周+激動(dòng)劑組、缺氧4周+抑制劑組和缺氧4周+生理鹽水組均在缺氧3周后,在缺氧艙內(nèi)腹腔注射給藥,第4周取得心臟。通過(guò)觀察心室質(zhì)量和心肌細(xì)胞面積比較心肌肥厚程度,小動(dòng)物心導(dǎo)管檢測(cè)心臟功能。結(jié)果 (1)臨床標(biāo)本中,相對(duì)于非紫紺組心肌,紫紺組的心肌面積明顯增加(P0.05),且伴隨著胞核、胞質(zhì)中β-catenin的蛋白表達(dá)減少。(2)小鼠慢性缺氧模型中,缺氧4周組明顯出現(xiàn)心肌細(xì)胞面積增加(P0.05),右心室與體質(zhì)量的比值增加(P0.05),右心射血分?jǐn)?shù)降低(P0.05),并伴隨著胞核、胞質(zhì)中β-catenin的蛋白表達(dá)減少。(3)與缺氧4周+生理鹽水組比較,缺氧4周+激動(dòng)劑組的心肌細(xì)胞面積減少(P0.05),右心室與體質(zhì)量的比值減少(P0.05),右心射血分?jǐn)?shù)增加(P0.05),胞核β-catenin水平和下游靶基因Cyclin D1表達(dá)水平明顯增加,而缺氧4周+抑制劑組無(wú)明顯變化(P0.05)。結(jié)論在慢性缺氧引起右心室肥厚過(guò)程中,β-catenin激活進(jìn)入胞核,能減輕心肌肥厚,并改善心臟功能。
[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.

【作者單位】： 樂(lè)山市人民醫(yī)院胸心外科;第三軍醫(yī)大學(xué)新橋醫(yī)院心血管外科;
【分類號(hào)】：R542.2
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本文編號(hào)：1638022