结核分枝杆菌低剂量感染小鼠模型的建立与分析

目的 建立结核分枝杆菌低剂量感染的小鼠模型，分析感染小鼠组织荷菌量、组织病理随感染时间的动态变化。 方法 以100 菌落形成单位(CFU)的结核分枝杆菌标准株H37Rv经尾静脉途径感染雌性C57BL/6J小鼠40只，于感染后1、3、5、8、12、16、20、24周取材，每个时间点5只小鼠，脾、肺组织匀浆培养检测脾脏组织的荷菌量，脾脏、肺脏及肝脏组织经HE染色分析病理变化。 结果 小鼠感染后3周脾脏荷菌量达到（4.97±0.19）lg CFU，在感染后5周下降至（3.64±0.22）lg CFU，至感染后8周降到最低的（2.75±0.23）lg CFU；感染后3周肝、脾、肺等脏器出现病理改变，感染5周时病变加重，感染8周时病变自然减轻。 结论 成功建立了结核分枝杆菌低剂量感染小鼠模型，为结核分枝杆菌慢性持续感染或潜伏感染的研究可提供有用的工具。

Establishment and analysis of a mouse model for low-dose Mycobacterium tuberculosis infection

Objective To establish a mouse model for low-dose Mycobacterium tuberculosis infection, and analyse the bacterial load and histopathological changes in the mouse tissues. Methods Forty C57BL/6J mice were infected intravenously with approximately 100 colony forming units (CFU) of M. tuberculosis H37Rv. Groups of five mice were euthanatized at 1, 3, 5, 8, 12, 16, 20 and 24 weeks after infection. The lungs and spleens were homogenized and plated to determine the bacterial load. Lungs, spleens and livers were fixed in buffered formalin and embedded in paraffin, and sections were prepared with haematoxylin and eosin to observe histopathological changes. Results Bacterial loads in spleens reached high level (4.97±0.19) lg CFU at 3 weeks after infection, then dropped to (3.64±0.22) lg CFU at 5 weeks after infection, and were minimized to (2.75±0.23) lg CFU at 8 weeks after infection. Pathological changes in the lungs, spleens and livers occurred at 3 weeks after infection, and aggravated at 5 weeks after infection, and were lessened naturally at 8 weeks after infection. Conclusion A mouse model infected with low-dose Mycobacterium tuberculosis was established successfully, and it might provide a base for the study of slow and persistence or latent M. tuberculosis infection.