转染人血红素加氧酶-1基因抑制移植静脉血管内膜增生

Human Heme Oxygenase-1 Gene Transfection Inhibits Intimal Hyperplasia of Vein Grafts in Rabbits

目的 应用含人血红素加氧酶 - 1基因 (human Heme Oxygenase- 1,h HO- 1)的重组腺病毒 (Adeno- XTMh HO- 1,Ad- h HO- 1)转染静脉移植血管 ,观察 h HO- 1基因预防静脉移植血管内膜增生的作用。 方法 将 2 1只日本大耳白兔分为 3组 ,对照组 ,Ad- null组和 Ad- h HO- 1组 ,每组各 7只。在兔颈外静脉移植于颈总动脉的血管移植术前分别应用肝素生理盐水、Ad- null和 Ad- h HO- 1病毒液常温浸泡静脉移植血管 30 min。术后 2 8d病理切片观察移植血管内膜增生的情况 ,计算机图象分析仪计算新生内膜厚度、中膜厚度及二者比值 ;采用免疫组织化学染色方法 (S- P法 )观察术后 14 d、2 8d移植血管壁 h HO- 1蛋白表达情况。 结果 Ad- h HO- 1组内膜厚度、内膜厚度与中膜厚度比均显著低于Ad- null组和对照组 (P<0 .0 1) ,中膜厚度差别无统计学意义 (P>0 .0 5 )。 Ad- h HO- 1组静脉血管壁细胞 h HO- 1免疫组化染色阳性。 结论 Ad- h HO- 1转染兔静脉旁路移植血管能够抑制内膜增生。

Objective To evaluate the effect of human heme oxygenase-1 augmentation in vein grafts by adenoviral-mediated gene transfer of heme oxygenase-1 （Ad-hHO-1） on intimal hyperplasia. Methods Twenty-one Japanese white rabbits were divided into three groups： control group, Ad-null control group, and Ad-hHO-1 group （each group 7 rabbits）. During the operation of rabbits jugular vein into carotid artery interposition grafting, harvested rabbit jugular vein segments were exposed for 30min at room temperature to heparin saline, recombinant replication deficient adenovirus encoding hHO-1 （Ad-hHO-1, 1× 10^9pfu/ml）, and nude recombinant replication deficient adenovirus （Ad-null, 1×10^9pfu/ml）. Quantitative histological studies of the vein segments were performed 28 days after operation. Protein of hHO-1 was detected with method of immunohistochemical staining（S-P） in 14 days and 28 days after operation. Results The average intimal thickness, medial thickness and intimal -to-medial （I/M） ratio were calculated for each group 28 days after bypass operation. Compared to intimal thickness, I/M ratio of control group veins and Ad-null group veins,Ad-hHO-1 group veins decreased significantly（P〈0.01）. There was no statistically difference in medial thickness （P〉0.05）. Strong staining of hHO-1 was detected in vein grafts wall of Ad-hHO-1 group. Conclusion Ad-hHO-1 gene therapy may inhibit intimal hyperplasia of vein grafts in rabbits.