Ad-HIF-1α-Trip转染兔缺血后肢的部分安全性研究  

Partial safety of Ad-HIF-1α-Trip gene transfection on a rabbit model of acute hind-limb ischemia

作　　者：何文凯[1] 李明琰[2] 崔永生[3] 陈建威[1] 王月刚[1] 陈冬冬[4] 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 [2]广州医科大学附属第一医院心内科,510120 [3]广州医科大学附属第四医院心内科,511447 [4]暨南大学附属华侨医院心内科,广州市510630

出　　处：《实用医学杂志》2014年第13期2028-2030,共3页The Journal of Practical Medicine

基　　金：广东省自然科学基金项目(编号:S2011010003151);广东省科技计划项目(编号:2011B031800286);国家自然科学基金(青年基金)项目(编号:81300086)

摘　　要：目的:探讨Ad-HIF-1α-Trip基因转染兔缺血后肢的部分安全性。方法:22只新西兰大白兔建立急性左后肢缺血模型,随机分为生理盐水组(Saline组,n=6)、腺病毒空载体组(Ad-Null组,n=6)、Ad-HIF-1α-Trip组(n=10)。分别在术后即刻肌注生理盐水、Ad-Null、Ad-HIF-1α-Trip。术后10 d Ad-HIF-1α-Trip组取4只行Real-time PCR了解HIF-1α-Trip转染后在缺血后肢及在心、肝、肾、肺的表达情况;术前、术后3 d、7 d、14 d、28 d,测量体温、体重,检测肝及肾功能、心肌酶;术后28 d对Ad-HIF-1α-Trip组心、肝、肾、肺进行HE染色,了解有无严重病理改变。结果 :转染后10 d,Ad-HIF-1α-Trip组缺血骨骼肌HIF-1α-Trip转染后有确切表达;心、肝、肾、肺未见表达。3组实验兔血常规、肝肾功能指标均在正常值范围,组间对比差异无统计学意义(P>0.05)。Ad-HIF-1α-Trip组心、肝、肾、肺HE染色未见明显异常。结论:Ad-HIF-1α-Trip单次肌肉注射能在兔缺血后肢明确表达,且未发现明显毒副反应。Objective To investigate the partial safety of the recombinant adenovirus containing the triple- point mutants HIF-1α gene （Ad-HIF-1α-Trip）transfection in a rabbit model of hind limb ischemia. Methods After ligation of left femoral artery, 22 New Zealand whites rabbits were randomly divided into 3 groups ： saline group （n = 6）, Ad-Null group（n = 6） and Ad-HIF-1α-Trip group（n = 10）. After operation, saline, Ad-Null and Ad-HIF- 1α were injected intramuscularly respectively. The expression of transferred HIF-1α at mRNA level in the ischemic skeletal muscle and other important organs were detected by Real-time PCR 10 days after gene transfection. The body temperature, weight, blood, liver and renal function, as well as the myocardial enzymes were detected before operation, and on the 3th, 7th, 14th and 28th day after gene transfection, so that pathological changes could be observed. Results On the 10th day after gene transfection, obvious expressions of HIF-1α at mRNA level in the ischemic limb were found, but no expression in other important organs was detected in Ad-HIF-1α-Trip group. The blood routine, liver and renal function were all in the normal range （P 〉 0.05）. No abnormalities were found in heart, liver, kidney, and lung HE transfection in Ad-HIF-1α-Trip group. Conclusion Single intramuscular injection of Ad-HIF-1α-Trip can be expressed obviously in the ischemic limb without detected damage of liver, cardiac and kidney.

关 键 词：Ad-HIF-1α-Trip 基因治疗 安全性 

分 类 号：R54[医药卫生—心血管疾病]