HIF-1α基因对心肌梗死后心肌细胞凋亡和心功能影响的实验研究

Effects of adenovirus mediated HIF-1α gene on myocyte apoptosis and cardiac function after myocardial infarction

目的:探讨腺病毒介导的低氧诱导因子-1α(HIF-1α)在急性心肌梗死(AMI)后对兔心肌细胞凋亡及心功能的影响。方法:复制兔AMI模型,随机分为4组,分别给心肌内注入腺病毒介导的HIF-1α基因(Ad-HIF-1α)、不含HIF-1α基因腺病毒颗粒(Ad-blank)、HIF-1α核酶基因(Rz-HIF-1α),假手术组(sham)为对照,各组动物分别在处死前应用Maclab/8s多功能生理仪记录不同时段心功能参数,末端原位标记(TUNEL)法检测心肌细胞凋亡。结果:凋亡细胞在sham组基本不存在,Rz-HIF-1α组最多,Ad-HIF-1α组少于Ad-blank组。1 d凋亡细胞最多,随着时间的延长,凋亡细胞逐渐减少,56 d仍有少量凋亡细胞存在。心功能参数sham组最高,Rz-HIF-1α组最低,Ad-HIF-1α组高于Ad-blank组。结论:腺病毒介导的HIF-1α基因治疗能明显减少心肌细胞凋亡,增强心功能,给予HIF-1α核酶基因则增加细胞凋亡,恶化心功能。

AIM ： To determine the effects of adenovirus mediated hypoxia - inducible factor -1α （ HIF -1α ） gene on myocyte apoptosis and cardiac function after acute myocardial infarction （AMI） of rabbits. METHODS ： Rabbits were made AMI model, divided into 4 groups at random and infected with Ad- HIF-1α, Ad -blank or Rz- HIF-1α, respectively. Sham group was served as control. The cardiac functions of rabbits at different time points were detected by Maclab/8s. Myocyte apoptosis was detected with TUNEL method at different time points. RESULTS： Apoptotic cells were the highest in Rz - HIF -1α treated group, less in Ad - HIF -1α treated group than that in Ad - blank group. Apoptotic cells decreased with extension of time and were found at the time of 56 d. The cardiac function parameters were the highest in sham, lowest in Rz - HIF -1α, and were higher in Ad - HIF -1α than those in Ad - blank. CONCLUSION ： Myocyte apoptosis is inhibited by Ad - HIF -1α, increased by Rz - HIF -1α. The cardiac function is improved by Ad - HIF -1α, deteriorated by Rz - HIF -1α.