腺病毒介导的人低氧诱导因子–1α治疗兔后肢缺血的安全性研究  

The safety of adenovirus-mediated hypoxia inducible factor- 1αfor rabbit hindlimb ischemia

作　　者：陈建威[1] 李明琰[1] 陈冬冬[1] 裴静娴[1] 王月刚[1] 吴平生[1] 

机构地区：[1]南方医科大学南方医院心内科,广州市510515

出　　处：《实用医学杂志》2010年第6期947-949,共3页The Journal of Practical Medicine

基　　金：国家自然科学基金资助项目(编号:30370587)

摘　　要：目的:对腺病毒介导的人低氧诱导因子-1α(Ad-HIF-1α)治疗兔急性后肢缺血的安全性进行探讨。方法:(1)Ad-HIF-1α及腺病毒空载体(Ad-Blank)扩增、滴度测定。(2)建立兔急性后肢缺血模型,随机分为3组,每组6只,分别以Ad-HIF-1α(2.0×1010PFU)、Ad-Blank(2.0×1010PFU)和NS(0.5mL)肌注离断股动脉肌群,观察兔一般反应,术前及术后7、28d检查心电图和血常规、肝肾功能,术后28d处死动物行病理学检查。结果:(1)Ad-HIF-1α及Ad-Blank滴度分别达2.0×1013、1.5×1013Pfu/mL。(2)受试期兔一般情况好;3组兔血常规、肝肾功能指标在正常值范围,组间对比无显著差异(P>0.05);心电图正常;病理学检查未见癌细胞。结论:兔急性后肢缺血模型局部一次性转染2.0×1010PFU的Ad-HIF-1α,未见明显毒副反应;Ad-HIF-1α应用于兔是相对安全的。Objective To explore the safety of human hypoxia inducible factor-1α （HIF-1α） for the rabbit model of acute hindlimb ischemia.Methods Adenovirus- mediated HIF-1α （Ad-HIF- lot） and adenovirus- mediated blank genes （Ad-Blank） were amplified and adenoviral titer was determined. A rabbit model of acute ischemic hindlimb was established and the rabbits were randomized to receive an injection of Ad- HIF-1α of 2.0×10^10 PFU,Ad-Blank of 2.0×10^10 PFU,or normal saline （NS） of 0.5mL into the muscle group without blood supply from femoral artery. ECG, blood test, and liver and renal function tests were performed before the procedure and on days 7 and 28. All the rabbits were observed pathologically on day 28. Results The titre of Ad-HIF-la was 2.0 ×10^13 Pfu/mL, and that of Ad-Blank was 1.5×10^13 Pfu/mL. Blood parameters and liver and kidney function were within the normal ranges in the three goups and there were no significant differences in those tests （P 〉 0.05）. ECG was normal. No cancer cells were seen in the rabbits receiving Ad- HIF-1α. Conclusions There are no significant adverse reactions in the rabbits with hindlimb ischemia receiving Ad-HIF-1α at a single dose of 2.0×10^10 PFU. Ad-HIF-1α is relatively safe.

关 键 词：缺血 安全性 基因治疗 腺病毒载体 低氧诱导因子-1Α 

分 类 号：R658[医药卫生—外科学]