重组鼠疫组分疫苗毒理学研究

目的研究重组鼠疫组分疫苗的毒理学作用以评价其安全性，为进一步临床研究提供实验依据。 方法对重组鼠疫组分疫苗进行急性毒性试验，将疫苗1次给予小鼠后，观察所产生的毒性反应和死亡情况，及小鼠对该药物的最大耐受量。分别进行小鼠和豚鼠的异常毒性试验，观察动物有无异常反应，7d后每只动物体重变化。进行家兔的局部刺激试验，注射给药后对动物和注射部位进行肉眼观察，取注射局部皮肤组织进行病理检查。进行豚鼠的全身过敏试验，将致敏的动物静脉快速注射攻击，观察豚鼠有无过敏症状。 结果2种浓度疫苗经腹腔和皮下2种途径注射小鼠，均未引起小鼠的异常症状和死亡，小鼠对重组鼠疫组分疫苗的最大耐受量大于10000μg／kg。小鼠和豚鼠的异常毒性试验表明，注射后7d每组动物均全部健存、无异常反应，且7d后每只动物体重均有增加，均符合2005年版《中华人民共和国药典》三部要求。局部刺激试验中疫苗对家兔注射局部皮肤未引起明显的组织病理学改变。全身过敏试验未出现任何异常反应。 结论重组鼠疫组分疫苗的急性毒性试验、异常毒性试验、局部刺激试验和全身过敏试验毒理学实验结果显示，重组鼠疫组分疫苗用皮下注射的途径进行免疫是安全的。

Studies of toxicology on recombinant plague vaccine

Objective To analyze the safety of recombinant plague vaccine and provide experimental support for clinical research. Methods Acute toxicity test was carried out .Mice were observed carefully after vaccination. Abnormal toxicity test was carried out in mice and guinea pigs. They were observed and weighed seven days after administration. Local stimulation was evaluated, through pathologic examination of local subcutaneous tissue of rabbits. Systematic anaphylaxis test was carried out in guinea pigs to evaluate the safety of recombinant plague vaccine. Results No abnormal symptom and death happened to mice in acute toxicity test. The maximum tolerable dose of recombinant plague vaccine for mice was more than 10 000 &;#61549;g/kg. There wasn’t any abnormal reaction happened in abnormal toxicity test. The weight of every animal increased seven days after administration. No pathologic change appeared after injection with recombinant plague vaccine. There was no abnormal reaction appeared in systematic anaphylaxis test. Conclusion The results of acute toxicity test,abnormal toxicity test,local stimulation test and systematic anaphylaxis test showed that subcutaneous injection of recombinant plague vaccine is safe, which provide a foundation for further clinical research.