分枝杆菌持续感染小鼠模型的建立及其特征分析

发布时间：2018-03-17 06:18

  本文选题：结核分枝杆菌　切入点：小鼠模型　出处：《中国病原生物学杂志》2017年03期 　论文类型：期刊论文

【摘要】：目的建立不同毒力的分枝杆菌持续感染小鼠模型并分析其免疫应答特征,为结核病新型疫苗及药物评价研究奠定基础。方法分别用结核分枝杆菌(Mtb)标准毒株H37Rv、减毒株H37Ra及疫苗株BCG经尾静脉注射感染BALB/c小鼠,5×10~4 CFU/只。感染后4、8周观察小鼠一般状态及体重变化;观察脾脏大体情况和肺组织病理改变;检测分枝杆菌特异性抗体水平、脾淋巴细胞刺激指数(SI)及Th1/Th2细胞因子分泌情况;采用平板计数法计脾、肺脏荷菌数CFUs。结果不同毒力分枝杆菌感染8周后,各组小鼠体重无显著差异;H37Rv感染组脾脏体积显著增大,肺组织病理切片显示菌株感染可引起不同程度的病理损伤;感染4周后小鼠血清特异性抗体水平升高,且感染后8周抗体水平高于4周水平,但不同菌株感染组间差异无统计学意义;不同毒力分枝杆菌感染小鼠的脾淋巴细胞刺激指数(SI)均升高,以H37Rv和H37Ra感染组脾淋巴细胞增殖更显著。H37Rv感染4周后IFN-γ、IL-10分泌水平显著升高(P0.05)。感染4周后,H37Rv小鼠脾脏荷菌数Log_(10)CFU显著高于BCG组,为4.389±0.1245,而H37Ra感染组与BCG组无显著差异,为4.068±0.2184;各感染组肺荷菌数Log_(10)CFU无显著差异;感染8周后,H37Ra、H37Rv感染组小鼠脾脏荷菌数显著高于BCG组(P0.05),而肺部荷菌数组间无差异。小鼠呈现持续感染状态。结论本研究成功建立了不同毒力分枝杆菌持续感染小鼠模型,该模型可用于结核病疫苗及药物的研发及筛选。
[Abstract]:Objective to establish a murine model with different virulence of Mycobacterium infection and to analyze its immune response. Methods the standard strain H37Rv of Mycobacterium tuberculosis, the attenuated strain H37Ra and the vaccine strain BCG were injected into the tail vein to infect BALB/c mice with 5 脳 10 ~ 4 CFU/. The mice were observed 48 weeks after infection. General state and weight change; Observe the general situation of spleen and pathological changes of lung tissue, detect the level of Mycobacterium specific antibody, spleen lymphocyte stimulating index (SI) and secretion of Th1/Th2 cytokines, calculate spleen by plate count method, Results after 8 weeks of infection with different virulent mycobacteria, the spleen volume of H37Rv infected mice was significantly increased, and the pathological sections of lung tissue showed that the infection could cause pathological damage to different degrees. After 4 weeks of infection, the serum specific antibody level of mice increased, and the antibody level of 8 weeks after infection was higher than that of 4 weeks, but there was no significant difference between different strains of infection groups. The spleen lymphocyte stimulating index (SI) of mice infected with different virulence mycobacteria increased, In H37Rv and H37Ra infected groups, the proliferation of spleen lymphocytes was more significant. The level of IL-10 secreted by IFN- 纬 was significantly increased 4 weeks after H37Rv infection. The Log_(10)CFU of spleen of H37Rv mice was significantly higher than that of BCG group (4.389 卤0.1245), but there was no significant difference between H37Ra infected group and BCG group. It was 4.068 卤0.2184.There was no significant difference in the number of Log_(10)CFU among the infected groups. After 8 weeks of infection, the spleen of mice infected with H37 Rahl H37Rv was significantly higher than that of BCG group (P 0.05), but there was no difference among the groups of pulmonary strains. The mice showed persistent infection status. Conclusion the mice model of persistent infection of different virulence mycobacteria was successfully established in this study. The model can be used for the development and screening of tuberculosis vaccines and drugs.
【作者单位】： 第四军医大学微生物学教研室;第四军医大学学员旅;
【基金】：国家"十二五"科技重大专项(No.2012ZX10003008-007) 国家自然科学基金面上项目(No.81371774,81671638) 第四军医大学本科生导师课题(No.2016011)
【分类号】：R-332;R516
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