高纯度蛇毒因子抗非协调性大鼠异种肝脏移植超急性排斥反应的机制研究

目的　探讨高纯度眼镜蛇毒因子 (CVF)对非协调性异种大鼠肝脏移植超急性排斥反应(HAR)和存活时间的影响及其机制。方法　实验分为CVF治疗组和对照组 ,每组各 2 0对。在豚鼠到大鼠肝脏移植前 2 4h实验组大鼠静脉注射CVF(5 0 μg/kg) ,异种肝脏移植后记录受体生存时间 ,并观察移植肝的病理变化 ,免疫荧光法检测肝脏血管C3沉积情况 ,用大鼠TNF αELISA试剂盒检测异种肝脏移植术后 1h血清中细胞因子TNF α水平。结果　肝脏移植后 ,对照组均发生了HAR ,肝内小血管血栓形成 ,间质出血 ,肝窦和中央静脉可见C3沉积 ,肠系膜淤血明显。实验组均无HAR发生 ,可见延迟性异种排斥反应 (DXR)的病理特征 ,血管内皮细胞 (EC)肿胀 ,单核细胞和中性粒细胞浸润 ,肝窦和中央静脉无C3沉积 ,肠道淤血不明显 ,血清TNF α水平下调 ,受体平均存活时间显著延长 (1 8±0 6与 7 4± 2 1h ,P <0 0 1)。结论　高纯度CVF清除补体可克服非协调性异种肝脏移植的HAR ,延长受体存活时间。CVF用于豚鼠到大鼠肝脏移植这一生命支持模型可以更深入地研究非协调性异种肝脏移植的相关机制

Mechanisms of purified cobra venom factor in preventing hyperacute rejection following discordant liver xenotransplantation in rats

OBJECTIVE: To investigate the mechanisms of purified cobra venom factor (CVF) in preventing hyperacute rejection (HAR) and prolonging recipient survival following discordant liver xenotransplantation in rats. METHODS: All animals were divided into two groups, group I (n = 20), unmodified recipients as control; group II (n = 20), xenograft recipients were treated with 50 microg/kg CVF i.v. on day-1. The pathologic changes of liver were observed and TNF-alpha of blood serum was detected. RESULTS: Recipient survival after CVF treatment is significantly prolonged compared with unmodified recipients (1.8 +/- 0.6 vs.7.4 +/- 2.1 h, P < 0.01). Histologically, widespread thrombosis, interstitial haemorrhage, C3 deposits on sinusoids and central veins characterized xenografts of the control group. Xenografts of the CVF group showed endothelium swelling and cellular infiltrate, no deposit of C3 was detected. CONCLUSION: Purified CVF can prevent guinea pig-to-rat liver xenografts from HAR and extend recipient survival. Preconditioning with CVF, guinea pig-to-rat combination is a useful life-supporting model to explore further mechanisms of discordant liver xenotransplantation.