移植物转染血红素氧合酶-1基因抑制慢性移植物血管病  

Graft transfected with HO-1 gene inhibiting graft arteriosclerosis in rat aortic transplants

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作  者:杜敦峰[1] 昌盛[1] 郭晖[1] 陈必成[1] 周鸿敏[1] 陈忠华 

机构地区:[1]华中科技大学同济医学院附属同济医院器官移植研究所,武汉430030

出  处:《中华器官移植杂志》2006年第1期44-48,共5页Chinese Journal of Organ Transplantation

摘  要:目的探讨移植物转染血红素氧合酶1(HO1)基因对慢性移植物血管病的影响。方法克隆HO1基因,并构建含有HO1基因的重组腺病毒载体(AdHO1),实验分为4组:A组为同系移植对照组,供、受者均为Lewis大鼠,无特殊处理;B组为同种移植对照组,Lewis大鼠接受未经处理的BN大鼠胸主动脉移植;C组为同种移植空载体对照组,Lewis大鼠接受以空载体(不含HO1基因)处理的BN大鼠的胸主动脉移植;D组为同种移植实验组,Lewis大鼠接受转染HO1基因的BN大鼠的胸主动脉移植。于移植后60d取移植动脉,进行组织形态学观察,测量内膜厚度;免疫组化和逆转录聚合酶链反应检测HO1在移植动脉中的表达。结果A组移植动脉形态正常;B组、C组移植动脉呈移植物血管病表现,血管内膜显著增厚,D组移植动脉呈内膜炎改变,内膜厚度与B组、C组相比,差异有统计学意义(P<0.01)。免疫组化及RTPCR检测显示,与A组、B组和C组相比,D组移植动脉可以检测到HO1基因及其蛋白表达。结论在移植血管中预先转染HO1基因,能明显缓解移植动脉的纤维化进程以及内膜的增生,对慢性排斥反应所致的移植物血管病具有抑制作用。Objective To investigate the efficacy of adenovirus mediated HO-1 gene transfer inhibiting graft arteriosclerosis in rat aorta transplantation model. Methods The PCR product of rat HO-1 cDNA was cloned into pShuttle-CMV vector, then pShuttle-HO-1 was cloned into pAdEasy-1 to construct recombinant vector pAd-HO-1. Transplantation was performed using inbred male Brown- Norway rats as donors and male Lewis rats as recipients. The descending thoracic aorta of donor was harvested and anastomosed to the recipient's abdominal aorta below the renal arteries and above the aortic bifurcation. The experiments was divided into 4 groups: Group A (Lewis-Lewis, n = 6) subject to no treatment; Group B (BN-Lewis, n = 6) subject to no treatment; Group C (BN-Lewis, n = 6), the aorta of donor was perfused with buffer containing Ad-Null;Group D (BN-Lewis, n = 6), the aorta of donor was perfused with buffer containing Ad-HO-1. The rats were sacrificed 60 days after the operation. The transplanted aorta was harvested. RT-PCR was performed to detect the expression of HO-1 gene. HE staining was used to detect the morphology and cytology of the transplanted vessels.Immunohistochemistry was used to detect the localization and expression of HO-1. Results Gene transfer of HO-1 into rat aortic grafts, using an adenoviral vector, resulted in the expression of HO-1 protein in endothelium and adventitial. Compared to group B and group C, neointimal formation 60 days after transplantation was inhibited in the aortic allograft transfected with HO-1 (P〈0. 01). Conchtsion Pre-transfection of the graft aorta with HO-1 gene can obviously inhibit the fibrosis progression and intimal hyperplasia of the transplanted artery and the development of graft arteriosclerosis caused by chronic rejection in the rat aortic transplant model.

关 键 词:移植物闭塞 血管 基因转移 血红素氧化酶 移植物排斥 

分 类 号:R654.2[医药卫生—外科学]

 

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