载脂蛋白A1-P11融合蛋白诱导血清抗体在大鼠、小鼠及家兔中的动态变化

目的探讨载脂蛋白A1-P11融合蛋白诱导血清抗体在大鼠、小鼠以及家兔中的变化,比较融合蛋白在三种动物中的反应原性,确定适于评价载脂蛋白A1-P11药效的动物种类。方法大鼠、小鼠及家兔各14只,随机选取7只按照1mg/kg体重静脉注射载脂蛋白A1-P11融合蛋白,隔天给药;各组余下的7只动物注射生理盐水作为对照。并在给药前1天、第2、4、8、12、15、18和20次给药时及停药后第1、2、3和4周采血。用酶联免疫吸附法检测不同时间点的中和抗体。结果载脂蛋白A1-P11在这三种动物中抗体变化的消长规律基本一致,但是家兔产生抗体显著高于小鼠和大鼠。结论三种动物中,大鼠和小鼠更适合作为评价载脂蛋白A1-P11长期功效的动物,因而这两种动物的病理模型可作为评价载脂蛋白A1-P11药效的候选动物,为探讨载脂蛋白A1-P11治疗高脂血症和干预动脉粥样硬化奠定基础。

Dynamic Change of Antibodies Induced by Apolipoprotein A1-P11 Fusion Protein in Rats,Mice and Rabbits

Aim To explore the dynamic change of antibobies in rats,mice and rabbits when they were treated with apolipoprotein A1-P11(ApoA1-P11) and the reactionogenicity of antibodies were compared among them,then to determine the suitable animal which can be repeately treated with ApoA1-P11 for long time.Methods 14 rats,14 mice and 14 rabbits were each randomly divided into two groups:the ApoA1-P11 group and the control group.The ApoA1-P11 group received ApoA1-P11(1 mg/kg weight,once every other day) respectively,and the control group received normal saline in the same way.The serums of both groups were collected before the administration,in the week 1,2,3 and 4 after the last injection.The chang pattern and titers of antibodies were determined by ELISA.Results The rising and dropping patterns of antibodies in rats,mice,and rabbits were similar,but the level of antibodies produced by rabbits was much higher than that of rats and mice.Conclusions The rats and mice are more suitable for evaluation of ApoA1-P11's effects for long-time use,to whom correspondance should be addressing compared with rabbits,which laid a foundtion for ApoA1-P11 used for treating hyperlipemia and atherosclerosis.