不同地域恒河猴感染H37Rv结核菌株的差异比较

Differences in Chinese rhesus macaques from different regions infected with Mycobacterium tuberculosis H37Rv

目的探讨不同地理分布的恒河猴亚种在结核分枝杆菌感染实验中的反应差异,为在结核疫苗评价中选择合适的动物模型提供依据。方法通过纤维支气管镜定量感染湖北、广西恒河猴,建立急性感染结核病模型。在不同的时间点检测血液、血生化(包括C反应蛋白)、血沉等指标,并对组织细菌载量、肺组织和淋巴结病理切片进行对比分析。结果湖北恒河猴的血液学指标在感染期间均呈下降趋势,在第16、20周(感染后期)均低于广西恒河猴,但血沉值在12、16、20周呈上升趋势,均高于广西恒河猴。两组恒河猴血液中性粒细胞在第12周(湖北猴1.1×1010/L,广西猴4.7×109/L)、淋巴细胞第4周(湖北猴1.7×109/L,广西猴6.8×109/L)和嗜碱性粒细胞在感染前(湖北猴4.3×107/L,广西猴2.0×108/L)差异有统计学意义(P<0.01),血小板在16周(湖北猴3.8×1011/L,广西猴4.5×109/L)、20周(湖北猴4.1×1011/L,广西猴4.9×109/L)差异有统计学意义(P<0.01)。湖北恒河猴左肺细菌载量(4.52lgCFU/g)低于广西恒河猴(6.30lgCFU/g)(P<0.05)。与广西恒河猴相比较,湖北恒河猴左、中、上肺有明显结核结节。结论在MTB的急性感染实验中,湖北和广西恒河猴的血液学指标、部分组织的细菌载量和病理改变均存在差异。

Objective To investigate differences in Chinese rhesus macaques from different regions infected with Mycobacterium tuberculosis in order to select an appropriate animal model for evaluation of M.tuberculosis vaccines. Methods Chinese rhesus macaques from Hubei and Guangxi were infected with the H37 Rv strain of M.tuberculosis via intratracheal instillation into the lungs in order to establish a model of acute tuberculosis.The macaques were clinically observed and laboratory tests were performed to determine hematologic parameters,biochemistry indices,and the erythrocyte sedimentation rate（ESR）.Histopathological assessments were performed in week 24post-infection.Statistical analysis of monkeys from the 2regions was performed using ANOVA. Results After infection,hematologic parameters declined in rhesus macaques from Hubei and were lower than those in rhesus macaques from Guangxi in week 16 and 20post-infection.However,the ESR in rhesus macaques from Hubei increased in week 12,16,and 20 and was higher than that in rhesus macaques from Guangxi.In both groups,neutrophil granulocytes（NEU）differed significantly（P〈0.01）in week12（1.1×1010/L for macaques from Hubei vs.4.7×10^9/L for macaques from Guangxi）,lymphocytes（LYM）differed significantly in week 4（1.7×10^9/L for macaques from Hubei vs.6.8×10^9/L for macaques from Guangxi）,and basophils（BASO）differed significantly from their level prior to infection（4.3×10^7/L for macaques from Hubei vs.2.0×108/L for macaques from Guangxi）.Rhesus macaques from Hubei had a significantly（P〈0.01）lower platelet count（PLT）in week 16（3.8×10^11/L for macaques from Hubei vs.4.1×10^11/L for macaques from Guangxi）and week 20（4.5×10^9/L for macaques from Hubei vs.4.9×10^9/L for macaques from Guangxi）post-infection.Rhesus macaques from Hubei had a significantly（P〈0.05）lower bacterial load（4.52lgCFU/g）in the left lung in comparison to that（6.30lgCFU/g）in rhesus macaques from Guangxi. Conclusion The hematologic parameters,the bacterial load,and the histopathology of the left lung differed significantly between rhesus macaques from Hubei and Guangxi in a model of acute tuberculosis.