文章摘要
郑 媛,侯道荣,付鹤玲,尹 媛,鲍 丹.转基因Tomoregulin⁃1低表达加速扩张型心肌病小鼠的病理进程[J].南京医科大学学报,2018,(9):1187~1191
转基因Tomoregulin⁃1低表达加速扩张型心肌病小鼠的病理进程
Transgenic low expression of Tomoregulin⁃1 accelerated dilated cardiomyopathy patholo⁃gical progress in mice
投稿时间:2017-07-03  
DOI:10.7655/NYDXBNS20180903
中文关键词: Tomoregulin⁃1  扩张型心肌病  转基因小鼠  纤维化
英文关键词: Tomoregulin⁃1  dilated cardiomyopathy(DCM)  transgenic mice  fibrosis
基金项目:南京医科大学科技发展基金重点项目(2016NJMUZD019)
作者单位
郑 媛 南京医科大学医药实验动物中心江苏 南京 211166 
侯道荣 南京医科大学医药实验动物中心江苏 南京 211166 
付鹤玲 南京医科大学医药实验动物中心江苏 南京 211166 
尹 媛 南京医科大学医药实验动物中心江苏 南京 211166 
鲍 丹 南京医科大学医药实验动物中心江苏 南京 211166 
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中文摘要:
      目的:探究Tomoregulin?1对扩张型心肌病(dilated cardiomyopathy,DCM)小鼠病理进程的影响。方法:Western blot方法检测Tomoregulin?1在cTnTR141W DCM小鼠模型心脏组织中的表达水平;于2、4和6月龄对同窝阴性(non?transgenic littermates,NTG)小鼠、心脏组织特异Tomoregulin?1低表达小鼠、cTnTR141W DCM小鼠和心脏组织特异Tomoregulin?1低表达×cTnTR141W双转基因(double transgenic,DTG)小鼠进行M型超声心动图和病理组织学表型分析。结果:Tomoregulin?1在cTnTR141W DCM小鼠模型心脏组织中表达显著增高;M型超声心动图显示,与NTG小鼠相比,心脏组织特异Tomoregulin?1低表达小鼠在2、4和6月龄时心脏均呈现显著的室壁变薄、心腔增大和心收缩功能减退的表型;与cTnTR141W DCM模型小鼠相比,DTG小鼠在2、4和6月龄时心脏均呈现显著的室壁变薄的表型,亦呈现心腔增大和心收缩功能减退的趋势;病理组织学显示,与NTG小鼠相比,心脏组织特异Tomoregulin?1低表达小鼠心肌细胞排列紊乱并出现间质纤维化的表型;与cTnTR141W DCM模型小鼠相比,DTG小鼠的心肌细胞排列紊乱和间质纤维化程度更加严重。结论:转基因低表达Tomoregulin?1加速了cTnTR141W DCM小鼠的病理进程,Tomoregulin?1可能是DCM调节的重要修饰基因。
英文摘要:
      Objective:To explore the effects of Tomoregulin?1 on dilated cardiomyopathy(DCM)pathological progress in mice. Methods:The expression level of Tomoregulin?1 in the heart of wild?type and cTnTR141W DCM transgenic mice was detected by Western blot. The phenotype analysis of the non?transgenic littermates(NTG),heart?specific Tomoregulin?1 knockdown(Tomoregulin?1?kd),cTnTR141W and heart?specific Tomoregulin?1?kd×cTnTR141W double transgenic(DTG) mice at 2,4 and 6 months of age were analyzed by M?mode echocardiography and histopathologic examination. Results:The expression of Tomoregulin?1 was significantly increased in the heart of cTnTR141W DCM transgenic mice. M?mode echocardiography showed that the heart?specific Tomoregulin?1?kd mice presented thin?walled ventricles,larger left ventricular diameters and decreased cardiac function at 2,4 and 6 months of age compared with the NTG mice. The DTG mice presented significantly thin?wall ventricles and the tendency of larger left ventricular diameters and decreased cardiac function at 2,4 and 6 months of age compared with the cTnTR141W DCM mice. Myocardial disarray and fibrosis were clearly observed in the heart tissues from the Tomoregulin?1?kd mice compared with the NTG mice. The DTG mice presented more serious pathological phenotype compared with the cTnTR141W DCM mice. Conclusion:Transgenic low expression of Tomoregulin?1 accelerated DCM pathological progress in mice. Tomoregulin?1 may be an important modifier gene of DCM.
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