结核分支杆菌Ag85A质粒DNA疫苗和抗结核药物联合治疗小鼠耐药结核病  

Therapeutic effects of Ag85A DNA vaccines combined with chemotherapy in a mouse model of MDR Mycobacterial tuberculosis infection

作　　者：梁艳[1] 吴雪琼[1] 张俊仙[1] 阳幼荣[1] 王兰[1] 李洪敏[1] 李忠明 史迎昌[1] 陆阳[1] 

机构地区：[1]中国人民解放军总医院第二附属医院结核病研究室,北京100091

出　　处：《广东医学》2007年第9期1398-1400,共3页Guangdong Medical Journal

基　　金：WHO基金资助项目(编号:V25-181-202);国家自然科学基金资助项目(编号:30070730);中国人民解放军总医院创新基金资助项目

摘　　要：目的研究结核分支杆菌Ag85A质粒DNA疫苗和抗结核药物联合治疗小鼠耐药结核病的效果。方法用结核分支杆菌高耐利福平低耐异烟肼临床分离株HB240尾静脉注射BALB/c小鼠1个月后,将小鼠随机分成两组,第一组用Ag85A质粒DNA疫苗治疗12周,第二组用利福平、异烟肼和结核分支杆菌Ag85A质粒DNA疫苗(免疫5次)联合治疗12周;治疗结束后4周,分别取肺、肝和脾观察病理改变、称取重量、做菌落计数。结果小鼠感染1个月后,肺内菌量可达到109CFU,脾内菌量达到107CFU。治疗结束后4周,第二组小鼠体重均超过第一组,肺、肝、脾脏指数(0.013,0.047,0.011)明显低于第一组(0.017,0.062,0.017),但差异无显著性(P>0.05)。第二组肺脏病变程度较轻,有2/4未见明显病变,脾脏均未见明显病变;而第一组脾脏仅1例未见明显病变。第二组小鼠肺内无菌生长,而第一组肺菌落数为1.2×106CFU;第二组小鼠脾菌落数为4.4×103CFU,比第一组脾菌落数(1.9×105CFU)减少了42倍。结论结核分支杆菌Ag85A质粒DNA疫苗和抗结核药物联合治疗小鼠耐药结核病比单纯疫苗治疗疗效明显。Objective To study the therapeutic effects of Ag85A DNA vaccines combined with chemotherapy in a mouse model of MDR mycobacterial tuberculosis infection. Methods BALB/c mice were infected with mycobacterial tuberculosis clinical HB240 strain resisting Isoniazid and Rifampin by intratail - vein injection for 4 weeks and were subsequently divided into tow groups. Mice of group 1 were treated with Ag85A DNA vaccines for 12 weeks. Mice of group 2 were treated with Ag85A DNA vaccines combined with INH and RIF, immunized five times every three weeks for 12 weeks. The lungs, livers and spleens were taken and their pathological changes, weight and number of mycobacterial colony were examined at 4 weeks after the end of treatment. Results After one month, the numbers of bacteria in the lungs and spleens of mice infected with mycobacterial tuberculosis clinical HB240 strain were up to 10^9 cfu and 10^7 cfu respectively. Four weeks after treatment, weight of mice in group 2 was significantly lower than that of group 1. Indexes of the lungs, livers and spleens （0, 013,0. 047,0. 011 ） of group 2 were lower than those of group 1 （0. 017,0. 062,0. 017） without significant difference（ P 〉 0. 05 ）. Four weeks after the end of treatment, lung lesion was milder in group 2. No lesions of lung were observed in 2 mice of group 2. No lesions of spleen were observed in the mice of group 2 and in 1 mice of group 1. No bacteria was observed in the lungs of group 2, but the numbers of bacteria in the lungs of group 1 were up to 1.2 × 10^6 CFU. The numbers of bacteria in the spleens of group 2 （4.4 × 10^3 CFU） was 42 times lower than that of group 1 （ 1.9× 10^5 CFU）. Conclusion The therapeutic efficacy is better in group 2 than that of group 1 in the mouse model of MDR mycobacterial tuberculosis infection.

关 键 词：DNA疫苗 分支杆菌 结核病 

分 类 号：R57[医药卫生—消化系统]