低氧诱导因子-1α小干扰质粒(siHIF-1α)抑制体内血管新生  

Hypoxia Inducible Factor-1α Interference on Anti-angiogenesis in vivo

作　　者：姜萌[1] 王彬尧[1] 王长谦[2] 何奔[1] 范华骅[3] 邵琴[1] 黄定九[1] 

机构地区：[1]上海交通大学医学院附属仁济医院心内科,上海200001 [2]上海交通大学医学院附属新华医院心内科,上海200092 [3]上海市血液中心,上海200051

出　　处：《标记免疫分析与临床》2008年第3期150-155,194,共7页Labeled Immunoassays and Clinical Medicine

摘　　要：本研究拟通过腺病毒感染法观察低氧诱导因子-1α(Hypoxia inducible factor-1α,HIF-1α)的干扰质粒在体内对新生血管的抑制作用。构建干扰性si RNA质粒(si HIF-1α),在体外通过腺病毒介导的方法将人si HIF-1α质粒(Ad-si HIF-1α)转入人外周血内皮祖细胞(endothelial progenitor cells,EPC);观察EPC的感染效率;确定病毒滴度;并将此Ad-si HIF-1αEPC移植至缺血下肢模型,观察对新生血管的抑制作用。结果显示Ad-si HIF-1α感染效率约80%,移植异种Ad-si HIF-1α-EPC至Balb/c鼠缺血下肢后发现干扰后的EPC在体内显著抑制缺血部位的HIF-1αmRNA及蛋白(P<0.05);Ad-si HIF-1α-EPC较对照组进一步抑制体内毛细血管数目(P<0.05);干扰组血流减慢,皮温降低(P<0.05),缺血局部细胞扩增减少(P<0.05)。表明Ad-si HIF-1α干扰后的EPC在体内可抑制缺血下肢的局部血管新生。This study was designed to explore the feasibility of anti-angiogenesis by Adeno-virus mediated Hypoxia inducible factor-1α（HIF-1α） interference in vivo. HIF-1α interference was constructed. Adeno-mediated siHIF-1α was transduced in human endothelial progenitor cells （EPC） in vitro. The infection rate and an ideal MOI were detected. After Ad-siHIF-1α EPC was transplanted into hind limb of ischemic Balb/c nude mice, the anti-angiogenesis in vivo was observed. The results showed that the infection efficiency was about 80%. HIF-1α mRNA and protein expression was dramatically and specifically down-regulated after adeno-siHIF-1α infection in cells. Neovascularization was hampered by adeno-siHIF-1α group not only in capillary but also in blood flow and temperature assessment （P〈0.05）. BrdU labeled cell proliferation showed decreased cell number in Ad-siHIF-1α EPC group. The results indicate that endothelial progenitor cells ex vivo modification by HIF-1α interference is feasible and may offer side-supply therapy in terms of tumor treatment.

关 键 词：低氧诱导因子-1Α 内皮祖细胞 缺血 血管新生 

分 类 号：R363[医药卫生—病理学]