本文選題：結(jié)核分枝桿菌　切入點(diǎn)：小鼠模型　出處：《中國(guó)病原生物學(xué)雜志》2017年03期 　論文類(lèi)型：期刊論文

【摘要】：目的建立不同毒力的分枝桿菌持續(xù)感染小鼠模型并分析其免疫應(yīng)答特征,為結(jié)核病新型疫苗及藥物評(píng)價(jià)研究奠定基礎(chǔ)。方法分別用結(jié)核分枝桿菌(Mtb)標(biāo)準(zhǔn)毒株H37Rv、減毒株H37Ra及疫苗株BCG經(jīng)尾靜脈注射感染BALB/c小鼠,5×10~4 CFU/只。感染后4、8周觀察小鼠一般狀態(tài)及體重變化;觀察脾臟大體情況和肺組織病理改變;檢測(cè)分枝桿菌特異性抗體水平、脾淋巴細(xì)胞刺激指數(shù)(SI)及Th1/Th2細(xì)胞因子分泌情況;采用平板計(jì)數(shù)法計(jì)脾、肺臟荷菌數(shù)CFUs。結(jié)果不同毒力分枝桿菌感染8周后,各組小鼠體重?zé)o顯著差異;H37Rv感染組脾臟體積顯著增大,肺組織病理切片顯示菌株感染可引起不同程度的病理?yè)p傷;感染4周后小鼠血清特異性抗體水平升高,且感染后8周抗體水平高于4周水平,但不同菌株感染組間差異無(wú)統(tǒng)計(jì)學(xué)意義;不同毒力分枝桿菌感染小鼠的脾淋巴細(xì)胞刺激指數(shù)(SI)均升高,以H37Rv和H37Ra感染組脾淋巴細(xì)胞增殖更顯著。H37Rv感染4周后IFN-γ、IL-10分泌水平顯著升高(P0.05)。感染4周后,H37Rv小鼠脾臟荷菌數(shù)Log_(10)CFU顯著高于BCG組,為4.389±0.1245,而H37Ra感染組與BCG組無(wú)顯著差異,為4.068±0.2184;各感染組肺荷菌數(shù)Log_(10)CFU無(wú)顯著差異;感染8周后,H37Ra、H37Rv感染組小鼠脾臟荷菌數(shù)顯著高于BCG組(P0.05),而肺部荷菌數(shù)組間無(wú)差異。小鼠呈現(xiàn)持續(xù)感染狀態(tài)。結(jié)論本研究成功建立了不同毒力分枝桿菌持續(xù)感染小鼠模型,該模型可用于結(jié)核病疫苗及藥物的研發(fā)及篩選。
[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- 緯 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 鹵0.1245), but there was no significant difference between H37Ra infected group and BCG group. It was 4.068 鹵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.
【作者單位】： 第四軍醫(yī)大學(xué)微生物學(xué)教研室;第四軍醫(yī)大學(xué)學(xué)員旅;
【基金】：國(guó)家"十二五"科技重大專(zhuān)項(xiàng)(No.2012ZX10003008-007) 國(guó)家自然科學(xué)基金面上項(xiàng)目(No.81371774,81671638) 第四軍醫(yī)大學(xué)本科生導(dǎo)師課題(No.2016011)
【分類(lèi)號(hào)】：R-332;R516
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本文編號(hào)：1623525