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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。
Objective To investigate the changes of serum antibodies induced by apolipoprotein A1-P11 fusion protein in rats, mice and rabbits and to compare the antigenicity of the fusion proteins in three kinds of animals and to determine the suitable apolipoprotein A1-P11 Effective animal species. Methods Fourteen rats, 14 rabbits and 14 rabbits were randomly selected. Seven rabbits were randomly assigned to receive 1 mg / kg body weight of apolipoprotein A1-P11 fusion protein intravenously. The remaining 7 animals in each group were injected with saline as control . Blood samples were taken on the 1st day, the 2nd, 4th, 8th, 12th, 15th, 18th and 20th doses, and the 1st, 2nd, 3rd and 4th weeks after drug withdrawal. Neutralizing antibodies at different time points were detected by enzyme-linked immunosorbent assay. Results The changes of the antibody changes of apolipoproteins A1-P11 in the three animals were basically the same, but the rabbits produced antibodies significantly higher than the mice and rats. Conclusions Rats and mice are more suitable as animals to evaluate the long-term effects of apolipoproteins A1-P11 in the three animals. Therefore, the pathological models of these two animals can be used as candidate animals for evaluating the pharmacodynamics of apolipoproteins A1-P11. To explore the apolipoprotein A1-P11 treatment of hyperlipidemia and intervention of atherosclerosis lay the foundation.