豚鼠结核病模型在抗结核新药评价中的应用

Guinea Pig Aerosol Infection Model in Evaluation of New Antitubercular Drugs

目的通过气溶胶感染构建豚鼠结核病模型，探讨其在新药评价中的应用。方法豚鼠以气溶胶方式感染结核杆菌，3周后随机分成不治疗组、异烟肼（isoniazid，INH）、莫西沙星（Moxifloxacin，Mfx）、氯法齐明（Clofazimine，cfz）、JYS—1和JYS-2两组进行药物治疗。治疗4周后解剖动物，观察体重、脏器重量指数、肺脏组织病理学检查及脾和肺活菌计数。结果INH、Mfx组的脾重指数、脾和肺荷菌量显著低于不治疗组（P〈0．05），肺部病变明显比空白组轻，而Cfz、JYS-1、JYS-2组各观察指标仅略优于不治疗组（P〉0．05）。结论通过气溶胶感染成功制备了豚鼠结核病模型，可对抗结核药物活性作出客观评价。

Objective To establish a guinea pig aerosol infection model and apply it to evaluate the anfitubercular activities of new drugs. Methods The guinea pigs were infected with H37Rv using the Glas-col inhalation exposure system. After infection of 3 weeks, animals were randomized into untreated group, isoniazid, Moxifloxacin, Clofazimine, JYS-1 and JYS-2 groups. All animals were sacrificed after 4 weeks of the treatment. The severity of infection and the effectiveness of the treatments were assessed by body weight, organ weight indices, pathological changes in lungs, and the numbers of CFU in the lungs and spleens. Results Both INH and Mfx treatments significantly reduced the organ weight indices, bacterial count and lung histopathology. While Cfz, JYS-1 and JYS-2 just exhibited small reduction in the organ weight indices, bacillary burden and lung histopathology. Conelusions Guinea pig aerosol infection model was established and enabled to objectively evaluate the new antitubercular activities of drugs.