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目的研究结核分枝杆菌DNA疫苗治疗小鼠耐多药结核病的效果。方法用结核分枝杆菌耐利福平和异烟肼临床分离株HB361尾静脉注射60只雌性BALB/c小鼠后,将小鼠随机均匀地分为6组,感染后第3 d开始,分别用生理盐水(A组)、pVAX1载体(B组)、利福平(C组)、HSP65DNA疫苗(D组)、Ag85A DNA疫苗(E组)、Ag85A/ESAT6嵌合DNA疫苗(F组)治疗60 d,DNA疫苗每隔15 d肌肉注射1次,共5次。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,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0.34、0.50和0.26 logs;脾脏菌落数依次减少了0.37、0.46和0.28 logs(P<0.05,P<0.01)。结论Ag85A DNA疫苗治疗小鼠耐多药结核病效果优于HSP65 DNA和Ag85A/ESAT6嵌合DNA疫苗。
Objective To study the effect of Mycobacterium tuberculosis DNA vaccine in treating MDR-TB in mice. Methods Sixty female BALB / c mice were inoculated into the tail vein of clinical isolates of Mycobacterium tuberculosis rifampicin and isoniazid inoculated with HB361. The mice were randomly divided into 6 groups randomly. The mice were sacrificed at day 3 after infection, (Group A), pVAX1 vector (group B), rifampicin (group C), HSP65 DNA vaccine (group D), Ag85A DNA vaccine (group E) and Ag85A / ESAT6 chimeric DNA vaccine d, DNA vaccine once every 15 d intramuscular injection, a total of 5 times. Three weeks after the treatment, lung and spleen were taken to observe the pathological changes, weighed, do colony count. Results Three weeks after the end of treatment, compared with the control group, the lung lesions in groups D, E and F were alleviated to some extent, and the lesions were limited. The normal alveolar structure was seen in 2/3 of the area. The outline of the alveolar was relatively clear and the cells were evenly distributed. Compared with group A, the number of lung colonies in group D, group E and group F decreased by 0.34, 0.50 and 0.26 logs, respectively; the spleen colonies decreased by 0.37, 0.46 and 0.28 logs in turn (P <0.05, P <0.01). Conclusion Ag85A DNA vaccine is superior to HSP65 DNA and Ag85A / ESAT6 chimeric DNA vaccine in the treatment of multidrug-resistant tuberculosis in mice.