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目的观察BCG-CpG-DNA对小鼠急性毒性和28d长期毒性作用,评价其一般毒性。方法小鼠分别经背部皮下给予BCG-CpG-DNA100、250和500μg1次(急性毒性试验)和7次(28d长期毒性试验),对照组注射生理盐水。单次给药后观察小鼠的生长情况和体重变化,14d后观察脏器是否发生病变;重复给药期间及末次给药后3周恢复期内,每周观察小鼠外观体征、局部刺激性和体重变化;末次给药后3d及3周检测血液学、血液生化学指标及主要脏器系数和抗双链DNA抗体水平。结果 BCG-CpG-DNA急性毒性试验中,各组小鼠均健康存活,体重增加,无毒性反应。BCG-CpG-DNA28d长期毒性试验中,动物体重、行为活动无异常,给药部位无局部刺激性表现;BCG-CpG-DNA重复给药可提高小鼠免疫细胞的数量;末次给药后3d,各试验组脾脏系数均高于对照组,且差异有统计学意义(P<0.05),经过3周恢复期回复正常;各试验组血清中抗双链DNA水平与对照组比较,差异无统计学意义,均低于25U/ml的临界值。结论 BCG-CpG-DNA主要影响小鼠的免疫细胞和免疫器官,未见其他明显的急性毒性和长期毒性作用,表明BCG-CpG-DNA具有较好的安全性。
Objective To observe the acute toxicity and long-term toxicity of BCG-CpG-DNA in mice for 28 days and evaluate its general toxicity. Methods Mice were injected with 100, 250 and 500μg of BCG-CpG-DNA subcutaneously once (acute toxicity test) and 7 times (long-term toxicity test of 28 days) respectively on the back of the mice. The control group was injected with normal saline. After a single administration, the growth and weight changes of the mice were observed. The lesions of the organs were observed after 14 days. During the repeated administration and the recovery period of 3 weeks after the last administration, the appearance signs and local irritation And body weight changes; hematology, blood biochemical indicators and major organ coefficient and anti-dsDNA antibody levels were measured 3d and 3 weeks after the last administration. Results In the acute toxicity test of BCG-CpG-DNA, all the mice in each group survived, gained weight and had no toxic reaction. In the long-term toxicity test of BCG-CpG-DNA28d, there was no abnormality in body weight and behavioral activity of animals, and there was no local irritation in the administration site. Repeated administration of BCG-CpG-DNA could increase the number of immune cells in mice. The spleen coefficient of each experimental group was higher than that of the control group, and the difference was statistically significant (P <0.05), returned to normal after 3 weeks of convalescence; anti-double-stranded DNA levels in each test group compared with the control group, the difference was not statistically significant Significance, are lower than the threshold of 25U / ml. Conclusion BCG-CpG-DNA mainly affects the immune cells and immune organs of mice, and no other obvious acute toxicity and long-term toxicity, indicating that BCG-CpG-DNA has good safety.