摘要
目的::探索在短时间内建立小鼠心肌内转基因后压力超负荷模型,为深入研究心脏肥大的分子机制提供可靠的实验对象。方法:雄性C57BL/6小鼠随机分为升主动脉缩窄组(手术组)和同期假手术组(对照组),手术组根据暂时阻断主动脉血流5s、10s、20s、30s同时左心腔内分别注射Ad-LacZ或PBS后又分为LacZ组和PBS组,观察术后4周不同时间小鼠体重、颈动脉血压和心脏超声等变化HE染色和X-gal染色分别观察心肌肥厚情况和基因转染情况。结果:手术成活率88.8%。升主动脉缩窄小鼠的血压较对照组明显升高。缩窄术后2周心肌明显肥厚,4周时出现失代偿性心力衰竭。X-gal染色显示阻断血流5s以上心脏有蓝染,但10s、20s、30s之间无明显区别。结论:该方法简单有效,重复性好,可在短时间内建立小鼠心肌内转基因和压力超负荷心肌肥厚模型,为心脏肥大的深入研究提供可靠的实验对象。左心室心腔直接注射转染Ad-LacZ基因同时阻断升主动脉血流10s以上可以使目的基因有较好的表达。
Objective：To establish the mice model of pressure overload induced by transverse aorta constriction（TAC） after intramyocardial transgene. Methods：Forty-four C57BI./6 male mice were randomly divided into transverse aorta constricted group （operated group） and sham-operated group （control group）. The operated group was divided into LacZ and PBS group after left ventricular injection of Ad-LacZ or PBS with temporarily blocking aortic blood flow for S, 10,20 and 30 s, respectively. The weight, carotid hlood pressure and cardiac coefficient were measured during 4 weeks after TAC. The thickness of left ventricular wall, heart function and left ventrieular inner diameter were measured hy echocardiography. The morphology of left ventricle and the degree of cardiac blue staining were observed by Hematoxylin-eosin and X-gal staining. Results： The overall survival rate was 88.8%. Compared with sham-operated group, the carotid blood pressure in constricted group was increased markedly after TAC （P〈0.01）. Left ventricular hypertrophy appeared in 2 weeks and heart failure in 4 weeks. The heart tissue appeared blue in models with aortic blood flow blocking for more than 5 s, whereas there was no difference among 10 s, 20 s and 30 s. Conclusion：It is a practical and reproducible model of pressure overload after intramyocardial transgene. The efficacy of gene expression may be better in mice with aortic blood flow blocking for more than 10s after left ventricular injection of Ad-LacZ.
出处
《中国临床医学》
北大核心
2007年第6期745-748,共4页
Chinese Journal of Clinical Medicine
基金
国家杰出青年科学基金项目(No.30525018)
上海市优秀学科带头人计划(No.05XD14003)
高等学校博士学科专项科研基金项目(No.20060246079)
留学回国人员科研启动基金项目。
关键词
升主动脉
心肌肥厚
小鼠
转基因
Ascending aorta
Cardiac hypertrophy
Mouse
Transgene
