噬菌体脂质体包被液治疗小鼠耐多药结核的初步研究

Effect of bateriophage liposome in mice infected by multi-drug resistant tuberculosis

目的:研究D29分枝杆菌噬菌体脂质体包被液对耐多药结核杆菌感染小鼠的治疗效果,探寻治疗耐多药结核病的新方法。方法:用超声波分散法把噬菌体制成脂质体包被液,对小鼠行气管切开法滴入106CFU.mL-1临床耐4药结核分枝菌悬液100μL制备动物模型,以利福平、异烟肼、链霉素、乙胺丁醇(H、R、S、E)联合治疗小鼠组为对照组,对试验组用噬菌体脂质体包被液雾化吸入治疗,剂量为106pfu.d-1。结果:体外实验表明:107pfu.mL-1D29悬液作用1 h达到最佳杀菌效果;小鼠在体实验中,噬菌体脂质体包被液治疗60 d转阴率为75%,治疗120 d转阴率87%;而抗结核病药治疗60 d转阴率为15%,治疗120 d转阴率35%。噬菌体治疗组的平均治愈率显著高于抗结核病药治疗组(81%vs 25%,P<0.05)。结论:噬菌体脂质体包被液对耐药结核菌感染小鼠具有良好的治疗效果,有可能成为治疗耐多药结核病的新方法。

Objective： To investigate the effect of the mycobacteriophage D29 liposome-coating liquid in the mice infected by multi-drug resistant tubercle bacillus （MDR-TB） , as a new method in treating multi-drug resistant tuberculosis. Methods： The mycobateriophage was entrapped into liposome-coating liquid with ultrasonic dispersion. Then, the tracheas of mice were excided and dropped with 106 CFU clinically drug-resistant tubercular ramose bacteria. The infected mice were treated with the phage liposome-coating liquid （106 pfu·d^-1） by atomized inhalation, and rifampicin （H）, rimifun （R） , streptomycin （S） and ethambutol （E） were applied as the controis. Results： In in vitro experiments, 107 pfu of D29 suspension attained the best bactericidal effect after 1-h exposure. In in vivo experiments, the curative rates were 75% and 87% , respectively, at 60 and 120 days after treatment with the phage liposome; while the curative rates were only 15% and 35% at 60 and 120 days after control treatments. The mean curative rate after mycobacteriophage D29 liposome-coating liquid was significantly higher than that after control treatments （ 81% vs 25 % , P 〈 0.05）. Conclusion ： Mycobacteriophage D29 liposome-coating liquid has a beneficial effect in mice infected by multi-drug resistant tubercle bacillus, which may be a new method in treating multi-drug resistant tuberculosis.