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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 effect of combination therapy of Mycobacterium tuberculosis Ag85A plasmid DNA vaccine with antituberculosis drugs in the treatment of drug-resistant tuberculosis in mice. Methods BALB / c mice were injected with tail vein of Mycobacterium tuberculosis high-resistant rifampin low-isoniazid clinical isolate HB240 for one month. Afterwards, the mice were randomly divided into two groups. The first group was treated with Ag85A plasmid DNA vaccine Weeks, the second group with rifampicin, isoniazid and Mycobacterium tuberculosis Ag85A plasmid DNA vaccine (immunized 5 times) combined treatment for 12 weeks; 4 weeks after treatment, respectively, to take the lung, liver and spleen pathological changes were observed, weighed Weight, do colony count. Results After 1 month of infection in mice, the amount of bacteria in the lungs reached 109 CFU and the amount of spleen bacteria reached 107 CFU. Four weeks after the treatment, the weight of the second group of mice was more than that of the first group. The index of lung, liver and spleen (0.013,0.047,0.011) was significantly lower than that of the first group (0.017,0.062,0.017), but the difference was not significant (P> 0.05). The second group of lung lesions lighter, 2/4 no obvious lesions, spleen no obvious lesions; the first group of spleen only 1 case no obvious lesions. The second group of mice developed aseptic growth in the lungs, with a first group of lung colonies of 1.2 × 10 6 CFU. The second group of mice spleen colonies was 4.4 × 10 3 CFU, which was lower than that of the first group (1.9 × 105 CFU) 42 times. Conclusion Mycobacterium tuberculosis Ag85A plasmid DNA vaccine and anti-tuberculosis drugs combined treatment of drug-resistant tuberculosis in mice than the vaccine treatment effect.