利福平依赖结核病小鼠模型的建立

目的建立利福平依赖结核病小鼠模型,为深入研究依赖结核病产生机制及其治疗提供技术平台。方法随机选取120只6-8周BALB/c小鼠,分为15组,采用临床分离结核菌利福平依赖株和敏感株以高低剂量分别感染BALB/c小鼠建立攻毒模型,以不同利福平给药频次治疗6周,观察小鼠体征、肺脾病变程度,测定肺脾重量指数、肺组织荷菌量及结核菌利福平依赖性。结果依赖株高剂量感染每周给药2次组病变程度重、范围广,肺、脾重量指数（WI）升高,肺组织荷菌量多,且87.5%分离株在含利福平2-10μg/ml的匡氏琼脂培养基中明显依赖利福平生长。结论采用临床分离的利福平依赖株,感染剂量在2×105-2×106CFU之间,给予每周2次利福平胃饲,持续6周,可形成稳定的利福平依赖结核病小鼠。

Establishment of rifampin-dependent mouse Mycobacterium tuberculosis model

Objective To establish the rifampin-dependent mouse Mycobacterium tuberculosis（M.tuberculosis）model.Methods One hundred and twenty BALB/c mice at the age 6-8 weeks were randomly divided into15 groups.Clinically isolated rifampin-dependent M.tuberculosis strains and drug-sensitive strains were used to establish an anti-poisoning model of BALB/c mice infected with a high or a low dose of M.tuberculosis.The mice were treated with rifampin for 6 weeks to observe their physical signs and pathological lesions in lungs and spleen.The weight index of lungs and spleen,bacterial load of lung tissue,and rifampin-dependence of M.tuberculosis strains were determined.Results The extent and areas of pathological lesions,the weight index of lungs and spleen,and the bacterial load of lung tissue were higher in mice infected with a high dose of M.tuberculosis after treatment with rifampin（twice a week）.Furthermore,87.5% isolated M.tuberculosis grew on Kuang′s agar medium containing 2-10μg/ml rifampin.Conclusion Rifampin-dependant M.tuberculosis strains can be isolated in clinic.The infection dose is 2×105-2×106CFU.A stable rifampin-dependent mouse model of tuberculosis can be induced by gastric rifampin for 6 weeks.