低氧诱导因子1α高表达对急性心肌梗死大鼠骨髓间充质干细胞的动员  

Hypoxia-inducible factor-1 alpha effects on bone marrow mesenchymal stem cell mobilization in rats with acute myocardial infarction

作　　者：戚金威[1,2] 程景林[1,2] 周姝[1,2] 李景荣[1,2] 李雪翔[1,2] 杨琴[1,2] 张浩[1,2] 万俊[1,2] 王育林[1,2] 张立新[1,2] 陈赟赟[1,2] 习秀霞[1,2] 叶丽[1,2] 唐茜[1,2] 徐凤[1,2] 江洋[1,2] 胡乐义[1,2] 刘泽岩[3] 

机构地区：[1]安徽医科大学第二附属医院急诊内科 [2]安徽医科大学第二临床学院急诊医学教研室,安徽省合肥市230000 [3]安徽医科大学研究生学院,安徽省合肥市230000

出　　处：《中国组织工程研究》2014年第10期1579-1584,共6页Chinese Journal of Tissue Engineering Research

基　　金：安徽医科大学高等学校自然科学基金项目(2012xkj065)~~

摘　　要：背景:设想通过增加自体干细胞动员达到有效修复心脏缺血区的目的,因此找到可利用的特异而有效的干细胞动员剂成为关键所在。目的:观察心肌梗死时低氧诱导因子1α表达对骨髓间充质干细胞动员的影响。方法:将90只远交群SD大鼠结扎冠状动脉前降支建立急性心肌梗死模型,随机分为3组:低氧诱导因子1α反义寡核苷酸组给予低氧诱导因子1α反义寡核苷酸干预抑制大鼠梗死缺血组织的低氧诱导因子1α的表达,低氧诱导因子1α错义寡核苷酸组和对照组分别给予等量低氧诱导因子1α错义寡核苷酸和生理盐水。结果与结论:造模后30 h、7 d,对照组外周血骨髓间充质干细胞计数及血浆血管内皮生长因子水平与低氧诱导因子1α错义寡核苷酸组相近,但明显高于低氧诱导因子1α反义寡核苷酸组。造模后7 d,对照组心肌缺血组织低氧诱导因子1α蛋白、血管内皮生长因子蛋白及mRNA表达与低氧诱导因子1α错义寡核苷酸组相近,但明显高于低氧诱导因子1α反义寡核苷酸组。造模后7,14,28 d,对照组心肌缺血组织切片毛细血管密度分析与低氧诱导因子1α错义寡核苷酸组相近,明显高于低氧诱导因子1α反义寡核苷酸组。说明大鼠急性心肌梗死后高表达的低氧诱导因子1α与骨髓间充质干细胞动员、启动一系列心肌组织自我修复过程有因果关系。BACKGROUND：Increasing autologous stem cellmobilization is conceived to achieve effectively repair of cardiac ischemic injury. Therefore, it is important to seek a specific and effective mobilization agent. OBJECTIVE：To observe the effects of hypoxia-inducible factor-1α（HIF-1α） on bone marrow mesenchymal stem cellmobilization in myocardial infarction. METHODS：Left anterior descending artery was ligated to establish a rat model of acute myocardial infarction in 90 outbreeding Sprague-Dawley rats, and then the models were randomly divided into three groups. In HIF-1α-antisense oligonucleotide （ASODN） group, HIF-1α-ASODN was infused into the tail vein to restrain the expression of HIF-1αin infarcted ischemic tissue. In HIF-1α-missense oligonucleotide （MSODN） group or control group, an equal volume of HIF-1α-MSODN or saline was injected. RESULTS AND CONCLUSION：After 30 hours and 7 days of modeling, the number of bone marrow mesenchymal stem cells and expression of vascular endothelial growth factor in the peripheral blood of the control group were similar to the HIF-1α-MSODN group, but significantly higher than the HIF-1α-ASODN group.＆amp;nbsp;After 7 days of modeling, the expressions of HIF-1αprotein, vascular endothelial growth factor protein and mRNA in the ischemic myocardial tissues of the control group were similar to the HIF-1α-MSODN group, but significantly higher than the HIF-1α-ASODN group. After 7, 14 and 28 days of modeling, the capil ary density in the ischemic myocardial tissues of the control group was similar to the HIF-1α-MSODN group, but significantly higher than the HIF-1α-ASODN group. These findings indicate that after acute myocardial infarction, high expression of HIF-1αexhibits a causal relationship with mobilization of bone marrow mesenchymal stem cells, initiating a series of self-healing process of myocardial tissues.

关 键 词：干细胞 骨髓干细胞 低氧诱导因子1Α 骨髓间充质干细胞 血管内皮生长因子 心肌梗死 动员 寡核苷酸 

分 类 号：R394.2[医药卫生—医学遗传学]