气溶胶感染小鼠急性结核病模型的建立及应用

目的建立气溶胶感染小鼠急性结核病模型,应用该模型评价抗结核新化合物的体内活性。方法应用气溶胶感染装置对BALB/C系小鼠进行不同浓度的H37Rv雾化感染,10d后应用抗结核药及新化合物开始治疗,给予15个剂量,在感染后3d、10d及30d分别进行小鼠解剖、肺活菌计数,统计分析该感染模型及药物的有效性。结果感染106cfu/ml的菌量可以较好的作为模型感染剂量,肺活菌计数和组织病理学结果均表明成功建立气溶胶感染小鼠急性结核病模型。INH治疗后肺活菌计数比较空白对照组可以降低5.95lgcfu,应用该模型筛选到新的抗结核活性化合物JYS-17。结论气溶胶感染小鼠急性模型适合抗结核新药早期活性筛选和评价。

Establishment and application of murine acute tuberculosis model by aerosol infection

Objective To establish and evaluate murine acute tuberculosis model by aerosol infection. Methods BALB/c mice were challenged with different doses of M. tuberculosis H37Rv by aerosol infection,and then treated for 15 doses by different compounds and drugs at 10 days after infection. At 3,10 and 30 days after infection,the lungs of the mice were homogenized,serially diluted,and plated on 7H11 agar plates for enumerating the bacterial load. The severity of infection and the effect of the treatments were assessed by body weight,gross lung lesions and clony forming unit （cfu） in the lungs. Results The cfu and histopathology in lungs of the mice showed that murine acute tuberculosis model were successfully established by aerosol infection. The 106cfu/ml of M. tuberculosis is suitable for this model. The treatment with Iisoniazid could reduce 5.95 lg cfu in comparison with that of untreated control at day 30 after infection. The active compound JYS-17 was screened out by the model. Conclusion Murine acute tuberculosis model by aerosol infection can be used for early evaluating anti-tuberculosis compounds and drug.