云南孟加拉种眼镜蛇蛇毒因子在灵长类动物内应用的免疫原性研究  

Immunogenicity of Yunnan-cobra Venom Factor in Non-human Primates

作　　者：向莹[1] 陈松[1] 李俊华[1] 钟山[1] 王婉瑜[2] 熊郁良[2] 陈实[1] 陈刚[1] 

机构地区：[1]华中科技大学同济医学院附属同济医院器官移植研究所,湖北武汉430032 [2]中国科学院昆明动物研究所动物毒素实验室,云南昆明650223

出　　处：《Zoological Research》2008年第5期511-517,共7页动物学研究（英文）

基　　金：国家自然科学基金资助项目(30500470)

摘　　要：眼镜蛇蛇毒因子(CVF)能特异性清除机体循环中的补体C3,从而可能在防治补体介导的损伤或疾病中发挥重要的治疗作用。云南孟加拉种眼镜蛇蛇毒因子(Y-CVF)较文献报道的其他各种CVF具有更高的活性和较少的用药量。为探讨Y-CVF静脉使用是否诱导灵长类动物体内产生特异性中和抗体和异种天然抗体,给2只正常食蟹猴每两周静脉注射一次治疗剂量(0.05mg/kg)的Y-CVF,共4次,检测注射前后不同时间点血清内补体C3水平、总补体活性(CH50)、抗Y-CVF抗体和抗猪内皮细胞异种抗体的变化。结果显示,前2次注射Y-CVF后均有良好的清除补体效果,第3次注射Y-CVF后补体仅被部分灭活,第4次注射Y-CVF后则基本无效。免疫印迹和酶联免疫吸附试验均证实特异性抗Y-CVF抗体产生,且其滴度随着Y-CVF注射次数增加而递增。多次注射Y-CVF后,并没有在血清内检测到明显的抗猪内皮细胞抗体的变化。因此,多次静脉注射Y-CVF能诱导灵长类动物产生特异性抗体,从而导致Y-CVF失效,但未发现抗α-Gal异种天然抗体明显增加。Cobra venom factor （CVF） depletes complement C3 and may therefore be important in preventing the complement-mediated damage and disease. In comparison with various CVF reported previously, Yunnan-cobra venom factor （Y-CVF） has higher anticomplement activity. The goal for this research is to investigate whether Y-CVF could induce the specific neutralized anti-Y-CVF antibody and xenoantibodies in non-human primates. Thus two cynomolgus monkeys were intravenously injected with Y-CVF （0.05mg/kg） every two weeks for totally four times. The serum C3, CH50, anti-Y-CVF antibody and xenoantibody levels were measured at different time points before and after Y-CVF injection. The results revealed that, complement C3 was effectively depleted during the first two injections, and incompletely depleted during the third injection, but almost not depleted during the last injection. The results of Western blot and EL1SA confirmed the production of anti-Y-CVF antibody, and its titer increased with the injection. Additionally no significant changes of anti-porcine endothelia cell xenoantibodies were found measured by flow cytometry. We concluded that multiple injection of Y-CVF stimulated anti-Y-CVF antibody production in monkeys, which resulted in the invalid of Y-CVF. The induction of anti-alpha -Gal xenoantibody by Y-CVF in primates was not observed.

关 键 词：食蟹猴 眼镜蛇蛇毒斟子 免疫原性 

分 类 号：Q51[生物学—生物化学]