摘要
采用颈部袖套血管吻合的方法(Heron法)可以建立稳定的豚鼠-SD大鼠非协调性异种异位心脏移植模型。应用中华眼镜蛇毒因子(cobra venom factor,CVF)清除受体的补体C3,可以成功克服异种超急性排斥反应(hyperacute xenogenetic refection,HAR),建立异种急性血管性排斥反应(acute xenograft vascular rejection,AVR)的模型。在成功建立模型的基础上,在供心冷缺血期间经冠状动脉缓慢灌注腺病毒表达载体介导血红素加氧酶-1(HO-1)基因进行转基因治疗,可以使外源性目的基因HO-1在供心成功转录,相关蛋白在移植心脏的心肌细胞和冠状动脉微血管内皮广泛表达,可以减少移植物内的炎性细胞浸润,保护内皮细胞,从而减轻免疫损害,明显延长异种移植物的存活时间。应用转基因技术导入保护性基因,从而保护移植物血管内皮细胞,减轻AVR对移植物的损害,可能是目前克服AVR的一种新策略。
Stable cervical cardiac xenotransplantation model of guinea pigs to SD rat was successfully established by Heron’s cuff vessel anastomosis technique. The usage of purified Chinese cobra venom factor administration showed excellent effects to exhaust complement C3 in rat recipient,can prevent discordant cardiac xenografts from hyperacute rejection(HAR) and establish the acute xenograft vascular rejection(AVR) model.On the base of the (AVR) model,Intracoronary perfusion of recombinant adenovirus vector ex vivo mediated heme oxygenase-1 gene transfer to guinea pig donor hearts during cold preservation after harvest,the method were efficient and effectively.The successful transcription of exogenous heme oxygenase-1 gene in the xenografts was confirmed. Extensive expression of exogenous gene in perivascular myocardial cell and coronary capillaries attenuated inflammatory cell infilitration in the xenografts, relieved impairment of immune reaction and significantly prolonged xenograft survival time. Gene transfer that can induce localized expression of exogenous gene and preserve the endothelial cell would be a new strategy for overcoming AVR.
引文
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