BCG-CpG-DNA重复给药对小鼠免疫毒性的初步评价  

Preliminary Evaluation on Immunotoxicity of Repeat Administration with BCG-CpG-DNA in Mice

作　　者：郑亮[1] 赵爱华[2] 王雯 乔来艳[2] 贾淑珍[2] 寇丽杰[2] 李凤祥[2] 吴小南[1] 王国治[2] 

机构地区：[1]福建医科大学公共卫生学院营养与保健医学系,福州350004 [2]中国药品生物制品检定所菌苗室,北京100050 [3]安徽龙科马生物制药有限公司,合肥230088

出　　处：《中国生物制品学杂志》2010年第9期922-925,929,共5页Chinese Journal of Biologicals

基　　金：十一五863课题(2006AA02A240)

摘　　要：目的观察BCG-CpG-DNA重复给药对小鼠免疫器官和免疫功能的影响,评价BCG-CpG-DNA的免疫毒性。方法将BALB/c小鼠随机分为4组,对照组注射生理盐水,实验组分别注射低(100μg)、中(250μg)、高(500μg)剂量的BCG-CpG-DNA,于28d内分别经背部皮下免疫7次,分别于初次免疫后14d、末次免疫后3d和3周,检测各组小鼠免疫器官脏器系数、淋巴细胞转化功能、细胞因子释放(ELISPOT法)、T细胞亚群变化(免疫荧光法)和NK细胞杀伤活性(乳酸脱氢酶法)。结果 BCG-CpG-DNA重复给药7次,主要影响小鼠初级免疫器官,表现为脾肿大,对胸腺、肝脏和肾脏无影响;对细胞免疫功能的影响是增强淋巴细胞转化功能;降低中、高剂量组CD3+T细胞亚群含量;提高体内分泌IFNγ和IL-4的细胞数二者的比例;增强NK细胞的杀伤能力。结论 BCG-CpG-DNA重复给药累计达3.5mg,小鼠表现为免疫功能增强,对免疫器官和免疫功能无不良影响,未见免疫毒性副作用。Objective To observe the effect of repeat administration with BCG-CpG-DNA on the immune organs and immune function of mice,and evaluate the immunotoxicity of BCG-CpG-DNA.Methods BALB /c mice were randomly divided into one control and three test groups.The mice in control group were injected s.c.with physiological saline,while those in three test groups with BCG-CpG-DNA at low（100 μg）,moderate（250 μg）and high（500 μg）dosages respectively,for 7 times within 28 d.The organ coefficient and lymphocyte transformation function of mice in various groups were evaluated 14 d after the first injection as well as 3 d and 3 weeks after the last injection,while the cytokine release was determined by ELISPOT method,the T lymphocyte subset by IFA,and the killing activity of NK cells by LDH method.Results The administration with BCG-CpG-DNA for 7 times mainly affected the immune organs of mice,expressed as splenomegaly,while showed no effect on thymus,liver or kidney.The repeat administration enhanced the lymphocyte transformation function,decreased the CD3＋ T lymphocyte subset counts in moderate and high dosage groups,increased the ratio of IFNγ-secreting cell count to IL-4-secreting cell count in vivo as well as the killing activity of NK cells.Conclusion Repeat administration with BCG-CpG-DNA to a cumulative dosage of 3.5 mg enhanced the immune function of mice while showed no adverse effect on immune organs or immune function,indicating no immunotoxicity.

关 键 词：BCG-CPG-DNA 免疫毒性 安全性评价 

分 类 号：R392-33[医药卫生—免疫学]