腺病毒介导的血红素氧合酶-1基因治疗对同种移植物慢性排斥反应损伤的保护作用

The protective effects on allografts of adeno-associated heme-oxygenase-1 gene therapy against chronic rejection injury

目的探讨腺病毒介导的血红素氧合酶-1(AdHO-1)基因治疗对同种移植物慢性排斥反应损伤的保护作用及其机制。方法选用血管移植和肾脏移植两种慢性排斥反应模型,对同种血管移植物和肾脏移植物进行体外 AdHO-1基因转染,分析慢性排斥反应发生时移植物的结构和功能变化、目的基因和蛋白的表达以及免疫系统的相应反应。结果 AdHO-1基因治疗缓解了慢性排斥反应对同种肾脏移植物的损伤,但弱于对血管移植物的保护效应;空载病毒加剧了同种。肾脏移植物的损伤;AdHO-1基因治疗可减少慢性排斥反应发生时移植物内巨噬细胞和 CD4^+细胞的浸润。结论AdHO-1基因治疗可能通过保护移植物、下调免疫反应、诱导免疫偏移等作用减轻同种移植物的慢性排斥反应损伤。

Objective To investigate the protective effects on allografts and the possible mechanism of adeno-asseciated heme-oxygenase-1 （ AdHO-1 ） gene therapy against chronic rejection injury. Methods Ex vivo AdHO-1 gene therapy was performed in vascular and renal transplantation models. The structure and function, the expression of therapeutic genes and proteins, and the immune modulation were analyzed. Results AdHO-1 gene therapy protected renal transplant against chronic rejection, but the effect was not as remarkable as that in vascular transplant. The transfected empty vehicle aggravated chronic rejection damage in renal transplantation. AdHO-1 decreased the infiltration of macrophages and CD4^ ＋ T cells. Conclusions AdHO-1 gene therapy can lessen damage of chronic rejection in allografts. It plays roles by protecting transplants, down-regulating immune response and inducing immune deviation.