结核分枝杆菌Ag85A质粒DNA疫苗治疗小鼠耐药结核病的效果研究

目的 研究结核分枝杆菌Ag85A质粒DNA疫苗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HB361尾静脉注射17～19 g的6～8周龄雌性BALB/c小鼠后,将小鼠随机均匀地分为6组,感染后第3天开始,分别用生理盐水(A组)、pVAX1空载体(B组)、利福平(C组)、微卡菌苗(D组)、Ag85A质粒DNA疫苗(E组)、利福平和Ag85A质粒DNA疫苗(F组)治疗60d,每组10只小鼠.治疗结束后3周,分别取肺和脾观察病理改变,称取重量做菌落计数.结果 治疗结束后3周,与对照组比较,D组、E组和F组肺脏病变有不同程度减轻,病变局限,病变范围分别为50%、20%、20%,2/3区域可见正常的肺泡结构,肺泡轮廓相对清晰,细胞分布均匀.与A组相比,D组、E组和F组肺脏菌落数分别减少了52%、68%、78%;脾脏菌落数依次减少了48%、65%、79%.结论 与对照组相比,Ag85A质粒DNA疫苗单独应用或与利福平联合应用治疗小鼠耐药结核病均显示疗效.

Therapeutic effects of Ag85A plasmid DNA vaccines in a mouse model of multi-drug resistant Mycobacterium tuberculosis infection

Objective To study the therapeutic effects of Ag85A plasmid DNA vaccines in a mouse model of multi-drug resistant-(MDR-) Mycobacterium tuberculosis infection. Methods BALB/c mice were infected with Mycobacterium tuberculosis clinical strain HB361 with isoniazid and rifampin resist-ance by intratail-vein injection and were subsequently divided into 6 groups. At the third day after infection, the mice were treated with saline (group A), vector pVAX1 (greup B), rifampin (group C), vaccae (group D), Ag85A plasmid DNA vaccines (group E),rifampin and Ag85A plasmid DNA vaccines (group F) for 60 d. The lungs and spleens from the mice were taken and their pathological changes, weight and number of myeobacterial colony were examined at the third week after the end of treatment. Results At third week af-ter the end of treatment, the gross pathological observation and histopathological examination in lung showed that the lung lesions were limited, the profile of the alveoli was relatively clear, and normal structure could be seen in 2/3 areas of the lung sections in group D, E and F. The extent of lung lesion was 50% in group D,20% in group E and F. The pathological changes in group A, B, and C were more severer than those in group D, E and F. Compared with group A, the colony-forming units (CFU) in the lungs from mice in group D,E and F decreased 52%, 68%, 78%, respectively. The CFU in the spleens from mice in group D,E and F decreased 48%, 65%, 79%, respectively. Conclusion Ag85A plasmid DNA vaccines alone or Ag85A plasmid DNA vaccines along with chemotherapy have significant therapeutic effects on the mouse model of MDR-Mycobacterium tuberculosis infection.