结核分枝杆菌Ag85A/ESAT-6嵌合型质粒DNA疫苗和抗结核药物联合治疗小鼠耐药结核病的效果研究  

Therapeutic effects of chimeric Ag85A/ESAT-6 DNA vaccines combined with chemotherapy in a mouse model infected with multi-drug resistant Mycobacterium tuberculosis

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] 

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所,北京100091

出　　处：《中国防痨杂志》2007年第5期382-385,共4页Chinese Journal of Antituberculosis

基　　金：WHO基金资助项目(V25-181-202);中国人民解放军总医院创新基金资助项目

摘　　要：目的研究结核分枝杆菌Ag85A/ESAT-6嵌合型质粒DNA疫苗和抗结核药物联合治疗小鼠耐药结核病的效果。方法用结核分枝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2组,第1组用利福平(RFP)、异烟肼(INH)治疗12周,第2组用RFP、INH和结核分枝杆菌Ag85A/ESAT-6嵌合型质粒DNA疫苗(免疫5次)联合治疗12周;治疗结束后4和8周,分别取肺、肝和脾观察病理改变、称取质量、作菌落计数。结果治疗结束后4和8周,第2组小鼠体质量均超过第1组,但无显著性差异(P>0.05)。治疗结束后4周,第2组肺、脾脏指数(0.017,0.011)均略低于第1组(0.020,0.012)(P>0.05);治疗结束后8周,第2组肺、肝脏指数(0.021,0.047)均略低于第1组(0.022,0.048)(P>0.05);而第2组脾脏指数(0.008)显著低于第1组(0.012)(P<0.05)。治疗结束后4周,第2组有4例脾脏未见明显病变,第1组仅1例脾脏未见明显病变;治疗结束后8周,第2组有1例肺门淋巴结肿大,而第1组有3例;第2组有5例脾脏未见明显病变,第1组仅2例脾脏未见明显病变。治疗结束后4周,第2组肺菌落计数和脾菌落计数比第1组显著减少,分别减少70%和80%。结论DNA疫苗和抗结核药物联合治疗小鼠耐药结核病疗效高于单纯化疗。Objective To study the therapeutic effects of chimeric Ag85A/ESAT-6 DNA vaccines combined with chemotherapy in a mouse model infected with multi-drug resistant （MDR） Mycobacterium tuberculosis. Methods BALB/c mice were infected by intravenous injection in a tail vein with Mycobacterium tuberculosis clinical isolate HB240 that is resistant to Isoniazid （INH） and Rifampin （RFP） for 4 weeks, and then were randomly divided into tow groups. The mice in group 1 were treated with RFP and INH for 12 weeks. The mice in group 2 were treated by chimeric Ag85A/ESAT-6 DNA vaccines combined with INH and RFP for 12 weeks. DNA vaccines were injected intramuscularly 5 times at 3 weeks intervals. The lungs, livers and spleens were taken and observed their pathological changes, weighted and performed mycobacteria cultures at 4 or 8 weeks after terminative treatment. Results At four and eight weeks after terminative treatment, the body weights of mice in group 2 were lower than that in group 1, but it had no significant difference（ P 〉 0.05）. At four weeks after terminative treatment, indexes of the lungs and spleens （0.017,0.011）from the mice in group 2 were lower than that in group 1 （0.020,0.012）. No swell of spleen could be observed in 1 mouse from group 2 and 4 mice from group 1. The numbers of bacteria in the lungs and spleens from mice in group 2 decreased 2.5 times and 4 times than those in group 1, respectively. At eight weeks after terminative treatment, indexes of the lungs and livers from the mice in group 2 （0.021,0.047）were lower than that in group 1 （0.022,0.048）（ P 〉 0.05）, but indexes of the spleens from the mice in group 2 （0.008）were significantly lower than that in group 1 （0.012）（ P 〈 0.05）. The swell of the lymph node of lung could be observed in 1 mouse from group 2 and 3 mice from group 1, no swell of spleen could be observed in 5 mice from group 2 and 2 mice from group 1. Conclusion The therapeutic efficacy of DNA vaccine combined with chemotherapy is str

关 键 词：DNA疫苗 分枝杆菌 结核 

分 类 号：R52[医药卫生—内科学]