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 pathological progress in mice

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cTnT^(R141W)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、cTnT^(R141W)DCM小鼠和心脏组织特异Tomoregulin-1低表达×c Tn TR141W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c Tn TR141WDCM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c Tn TR141WDCM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cTnT^(R141W)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cTnT^(R141W)DCM小鼠的病理进程,Tomoregulin-1可能是DCM调节的重要修饰基因。

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 cTnT^R141W 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）, cTnT^R141W and heart-specific Tomoregulin-1-kdxcTnT^R141W 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 cTnT^R141W 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 cTnT^R141W 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 cTnT^R141W 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.