低氧诱导因子1α抑制大鼠缺血下肢血管生成及内皮祖细胞的动员  

The inhibitory effect of hypoxia-inducible factor-1α on angiogenesis and endothelial progenitor cell mobilization after rat hind limb ischemia

作　　者：周健[1] 黄岚[1] 晋军[1] 武晓静[1] 方玉强[1] 宋明宝[1] 赵刚[1] 赵晓辉[1] 

机构地区：[1]第三军医大学新桥医院心内科,重庆400037

出　　处：《中华老年心脑血管病杂志》2006年第7期474-477,共4页Chinese Journal of Geriatric Heart,Brain and Vessel Diseases

基　　金：国家自然科学基金(30270568)

摘　　要：目的探讨低氧诱导因子1α(HIF-1α)在组织缺血时血管生成及内皮祖细胞(EPCs)动员中的作用。方法SD雌性大鼠36只,随机分为下肢缺血加HIF-1α反义寡核苷酸组(HIF-1α反义寡核苷酸组)、下肢缺血加HIF-1α错义寡核苷酸组(HIF-1α错义寡核苷酸组)和单纯下肢缺血组,每组12只,于股动脉结扎建立下肢缺血模型,缺血局部微注射脂质体转染的全硫代修饰HIF-1α寡核苷酸。测血浆血管内皮生长因子(VEGF);acLDL-DiI和FITC-UEA-I双染色鉴定EPCs后计数;下肢缺血区肌肉组织测HIF-1αmRNA和VEGF mRNA的表达和术后28天缺血区肌肉组织毛细血管密度。结果HIF-1α反义寡核苷酸组的HIF-1αmRNA和VEGF mRNA表达均较单纯下肢缺血组和HIF-1α错义寡核苷酸组明显减少;HIF-1α反义寡核苷酸组的循环EPCs、血浆VEGF及缺血区肌肉组织毛细血管密度均较单纯下肢缺血组和HIF-1α错义寡核苷酸组明显减少。结论全硫代修饰HIF-1α反义寡核苷酸可抑制大鼠缺血肢体血管生成和因缺血引起的EPCs的动员,其机制可能是通过VEGF起作用,HIF-1α是组织缺血时EPCs一个动员因子。Objective To study the effect of hypoxia-inducible factor- 1 α（ HIF- 1 α） on angiogenesis and endothelial progenitor cell（EPCs） mobilization during tissue ischemia. Methods Thirty-six rats were randomly divided into three groups：hind limb ischemia group, hind limb ischemia plus HIF-1α antisense oligonucleotide group and hind limb ischemia plus HIF-1α missense oligonucleotide group. Hind limb ischemia model was established by ligation of femoral artery. On the 7th day after operation and treatment with HIF-1α oligonucleotide, HIF-1α mRNA and VEGF mRNA were measured by RT-PCR. Circulating EPCs and plasma VEGF were also measured. Twenty-eight days after the operation, capillary density was measured in ischemic muscles. Results Compared with the hind limb ischemia group and hind limb ischemia plus HIF-1α missense oligonucleotide group, the expression of HIF-1α mRNA and VEGF mRNA, circulating EPCs and capillary density were decreased in hind limb ischemia plus HIF-1α antisense oligonucleotide group. Conclusions HIF-1α antisense oligonucleotide can inhibit angiogenesis and circulating endothelial progenitor cell mobilization in rat hind limb ischemia through regulating role of the VEGF. HIF-1α is a mobilization factor of EPCs during tissue ischemia.

关 键 词：缺血 血管生成因子 寡核苷酸类 反义 腿 大鼠 

分 类 号：R543[医药卫生—心血管疾病]