心脏组织特异性表达Neuregulin-2转基因小鼠的建立及心脏功能分析

发布时间：2018-04-22 21:04

本文选题：NRG + 转基因　；参考：《中国比较医学杂志》2014年03期

【摘要】：目的神经调节蛋白2(neuregulin-2,NRG2)可促进神经系统发育,基因缺失表现早期生长延迟,NRG2在心脏中也有表达,但其在心脏发育尤其是病理刺激时对心脏结构及功能的影响尚未见报道。本文目的是建立心脏组织特异性表达NRG2转基因小鼠,分析其在正常及压力负荷刺激时对心脏结构及功能的影响。方法将人NRG2基因插入到心脏特异性启动子α-MHC下游,构建转基因表达载体,显微注射法建立NRG2转基因小鼠,PCR鉴定转基因小鼠基因型,western blot鉴定NRG2蛋白在心脏中的表达并筛选高表达的转基因品系,主动脉缩窄术(transverse aortic constriction,TAC)制备压力负荷诱导的心肌肥厚小鼠模型。利用超声影像分析和病理学观察小鼠心脏结构和功能改变。结果建立了心脏组织特异性高表达NRG2转基因小鼠品系。与同窝阴性转基因小鼠相比,转基因小鼠左心室舒张末期后壁厚度(LVPWD)明显增加,3月龄时可达15.6%(P0.05),经压力负荷刺激后,NRG2转基因手术小鼠心室壁增厚程度显著下降,心室腔增大,同时心肌排列紊乱程度和纤维化程度明显比NTG手术小鼠严重。结论在压力负荷下,转基因表达NRG2缩短了肥厚过程,同时加速了心衰进程。
[Abstract]:Objective Neuroregulatory protein 2neuregulin-2 (NRG2) can promote the development of nervous system, and the expression of NRG2 is also found in the heart. However, the effect of NRG2 on the structure and function of the heart during cardiac development, especially during pathological stimulation, has not been reported. The aim of this study was to establish NRG2 transgenic mice with specific expression in heart tissue and to analyze its effects on cardiac structure and function during normal and pressure stress stimulation. Methods Human NRG2 gene was inserted into the downstream of heart specific promoter 伪 -MHC, and the expression vector was constructed. NRG2 transgenic mice were established by microinjection to identify the expression of NRG2 protein in the heart by western blot and to screen the transgenic lines with high expression. The rat model of myocardial hypertrophy induced by pressure load was established by transverse aortic constriction. The changes of heart structure and function in mice were observed by ultrasound image analysis and pathology. Results the cardiac tissue specific high expression NRG2 transgenic mice strain was established. Compared with the same litter negative transgenic mice, left ventricular posterior wall thickness (LVPWD) of transgenic mice increased significantly at the age of 3 months. The thickness of ventricular wall and ventricular cavity of NRG2 transgenic mice were significantly decreased after pressure load stimulation. At the same time, the degree of myocardial disarrangement and fibrosis was significantly more serious than that of NTG operated mice. Conclusion under pressure load, the expression of NRG2 shortens the hypertrophy process and accelerates the progression of heart failure.
【作者单位】：中国医学科学院医学实验动物研究所北京协和医学院比较医学中心卫生部人类疾病比较医学重点实验室;
【基金】：国家科技支撑计划课题(2012BA139B02)
【分类号】：R541

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