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  

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

作　　者：李正东[1] 石长清[1] 张群华[1] 熊郁良[2] 周兴丁[2] 王婉瑜[2] 宋宁[1] 

机构地区：[1]复旦大学华山医院复旦大学器官移植研究所,上海200040 [2]中国科学院昆明动物

出　　处：《中华医学杂志》2004年第23期2007-2010,共4页National Medical Journal of China

基　　金：上海市科委重点基金资助项目 (98XD14 0 0 2 );云南省应用基础研究基金重点项目 (2 0 0 0C0 0 0 7Z)

摘　　要：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。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; groupⅡ(n=20), xenograft recipients were treated with 50μg /kg CVF i v on day-1 The pathologic changes of liver were observed and TNF-α 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

关 键 词：蛇毒因子 大鼠 异种肝脏移植 超急性排斥反应 补体灭活剂 

分 类 号：R657.3[医药卫生—外科学]