心肌组织特异性Isca1敲除造成新生大鼠心脏结构异常

Isca1 myocardial conditional knockout results in cardiac structural abnormalities in newborn rats

目的通过对心肌组织特异性Isca1敲除大鼠进行磁共振分析及病理学分析,探究心肌特异性敲除Isca1对大鼠心脏结构影响。方法繁育心肌组织特异性Isca1敲除大鼠,PCR技术鉴定大鼠基因型及基因敲除效率,对新出生0.5d及2.5d心肌组织特异性Isca1敲除大鼠进行核磁共振影像分析,对新出生2.5d心肌组织特异性Isca1敲除大鼠心肌组织进行H&E染色及透射电镜分析。结果心肌组织特异性Isca1敲除大鼠敲除效率大于78%;与野生型相比,0.5d心肌组织特异性Isca1敲除大鼠心脏未见显著扩张;2.5d心肌组织特异性Isca1敲除大鼠心脏右室呈扩张趋势;2.5d心肌组织特异性Isca1敲除大鼠肌纤维排列不齐,出现排列紊乱,无层次或极向,部分心肌纤维出现溶解断裂,肌节和Z线模糊,出现肌膜损伤,线粒体嵴断裂,肿胀明显。结论心肌组织特异性Isca1敲除造成新生大鼠心脏结构异常。

Objective Magnetic resonance imaging (MRI) and pathological analysis were performed on Isca 1 myocardial conditional knockout rats to explore whether Isca 1 myocardial conditional knockout elicits abnormal cardiac structures in newborn rats.Methods Bred Isca 1 myocardial conditional knockout rats and the genotyping and knockout efficiency of Isca 1 were verified by PCR.MRI was performed on the postnatal 0.5 d and 2.5 d Isca 1 myocardial conditional knockout rats.Pathological examination using H&E staining and transmission electron microscopy were performed on the myocardial tissues of postnatal 2.5 d Isca 1 myocardial conditional knockout rats.Results The knockout efficiency of Isca 1 myocardial conditional knockout rats was more than 78%.Compared with wild type rats,the 0.5 d Isca 1 myocardial conditional knockout rats showed no significant dilatation;however,the right ventricles of 2.5 d Isca 1 myocardial conditional knockout rats showed a tendency to dilate.Moreover,the myocardial fibers of 2.5 d Isca 1 myocardial conditional knockout rats were irregularly arranged and disordered losing hierarchy or polarity.Part of the myocardial fibers showed dissolution and rupture.In addition,the sarcomere and Z-line were blurred,the sarcolemma was damaged,with mitochondrial swelling and rupture of cristae.Conclusion Isca 1 myocardial conditional knockout results in abnormal cardiac structures in newborn rats.