中文摘要：

目的研究结核分枝杆菌Ag85A／ESAT-6嵌合基因DNA疫苗及其与抗痨药物联合治疗小鼠结核病的效果。方法用结核分枝杆菌临床分离的利福平和异烟肼敏感株HB240-1尾静脉注射17～19g的6～8周龄雌性BALB／c小鼠后，将小鼠随机均匀地分为5组，感染后第3d开始，分别用pVAX1空载体（A组）、利福平和异烟肼（B组）、利福平、异烟肼和Ag85A／ESA-6嵌合基因DNA疫苗（C组）、Ag85A／ESAT-6嵌合基因DNA疫苗（D组）、HSP65基因DNA疫苗（E组）治疗40d，每组10只小鼠。治疗结束后2w，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5w后，肺内菌量可达到1．8×10^6CFU，脾内菌量达到1．7×10^6CFU。治疗结束后2w，B组和C组肺、脾脏器重量指数显著低于D组和E组，D组和E组脾脏器重量指数低于A组，但差别不显著。A组肺脏病变程度最重，病变范围80％～100％，干酪样坏死灶为弥漫性；D组和E组肺脏病变范围50％，干酪样坏死灶为片状；B组和C组肺脏病变程度较轻，病变范围较小，干酪样坏死灶为点状。A组脾脏9只重度肿大；B组和C组脾脏未见明显病变；D组和E组脾脏各有4只重度肿大。与A组相比，E组、D组、B组和C组肺脏菌落数分别减少了45％、50％、98．9％、99％；脾脏菌落数依次减少了50％、55％、99．2％、98．4％。与pVAX1空载体治疗组相比，各治疗组均有不同程度的疗效，Ag85A／ESAT-6嵌合基因疫苗组与HSP65基因疫苗组疗效相当。结论Ag85A／ESAT-6嵌合基因DNA疫苗组联合化疗的疗效明显强于Ag85A／ESAT6嵌合基因DNA疫苗单独应用。

英文摘要：

To investigate the therapeutic effect of the chimrtic DNA vaccine combined with chemotherapy,BALB/c mice were infected with the clinic isolate strain of M. tuberculosis HB240-1 through intra-tail vein, and were subsequently divided into 5 groups for experimentation. On the third day after infection,mice were treated with plasmid DNA vector（A） ,rifampin and isoniazid（B） ,rifampin,isoniazid and chimeric plasmid DNA vaccine Ag85A/ESAT-6（C）,chimeric plasmid DNA vaccine（D）or HSP-65 plasmid vaccine（E） for 40 days. Two weeks after the end of treatment,lungs,liver and spleen of mice were taken for pathologic examination and colony counting. It was found that the numbers of bacteria in lungs and spleen infected with M. tuberculosis HB240-1 strain 5 weeks after infection approached up to 1.8 × 10^6 CFU and 1. 7 × 10^6 CFU repectively. The weight indices of lungs and spleen of group B and C were significantly lower than those of group D and E two weeks after the end of treatment,whereas the weight indices of spleen of group D and E were lower than that of group A;however no significant difference existed. As to the lesions in lungs,they were mild in intensity in group B and C, medium in group D and E,but severe in group A. The extent of lesions in lungs of group A was 80% to 100% with diffuse canceous necrosis;50% in group D and E with caceous necrosis of plaque shape, the lung lesions in group B and C were rather mild only with small amount of lesions. Severe swelling of spleen was observed in 9 mice of group A, 4 mice in group D and E, but no spleen swelling in group B and C. Compared with group A,the numbers of bacteria in lungs of mice of groups E, D, B and C decreased to 45 %, 50%,98. 9% and 99% respectively, and those in spleens of these groups of mice decreased to 50%,55% ,99.2% and 98.4% respectively. It is evident that in comparison with the plasmid vector group,the treatment groups mentioned in the present study all showed different degrees of therapeutic efficiency and the therapeutic effici