清除补体避免猪到猕猴异种心脏移植超急性排斥反应的实验研究

目的 观察纯化的眼镜蛇毒因子(CVF)对猪到狱猴异种心脏移植超急性排斥反应的影响。方法 以幼猪为供者，施行猪到狱猴腹腔内异位心脏移植，实验组(n＝4)使用CVF完全清除受者体内补体，对照组(n＝5)不使用CVF，两个组术后均采用环抱素A、甲泼尼龙和环磷酰胺抑制排斥反应，通过检测血清C3、C4水平及总补体活性验证CVF的效果，移植心停跳时切取移植心进行病理检查。结果 在使用CVF后，实验组血清C3降为0，总补体活性CH50值也几乎为0，末发现明显毒副反应，移植猪心存活时间平均为lld，最长达13d，病理学提示均发生了延迟性异种排斥反应；对照组3个移植心在移植后60min内发生超急性排斥反应，另2个分别存活22h及6d。结论 纯化的CVF有良好的清除补体的作用，且末见明显副作用；使用CVF可克服猪到狱猴异种心脏移植超急性排斥反应的发生。

Prevention of hyperacute rejection of pig-to-monkey cardiac xenografts by depletion of complement

Objective To investigate the efficacy of cobra venom factor (CVF) in preventing hyperacute rejection (HAR) after pig to monkey heart xenotransplantation.Methods Heterotopic xenogeneic heart transplantation in the abdominal cavity was performed using piglets as donors. Nine monkeys (macaca mulatta) were used as recipients and were immunosuppressed with a combination of cyclosporine, cyclophosphamide, and steroids. Complete complement depletion was achieved in 4 of the recipients with CVF. In control group, 5 monkeys were not treated with CVF. All recipients underwent regular blood sampling for C3, C4 levels and complement activity. The xenografts were excised for histopathological examination when no myocardial contractions could be seen or felt. Results In 4 recipients receiving CVF therapy, C3 was completely depleted and no side effect due to CVF was found. The pig hearts'survival ranged from 8 to 13 days, with an average survival of 11 days. The grafts showed histopathologic features of delayed xenograft rejection (DXR). But in control group, 3 of 5 pig hearts were hyperacutely rejected after 15 to 60 min, and the remaining 2 survived for 22 h and 6 days respectively.Conclusion The CVF used showed an excellent effect to deplete complement completely and no obvious toxic effect could be seen. CVF prevented HAR after discordant xenotransplantation. Not all control hearts underwent HAR.