目的 建立布鲁菌液体气溶胶感染小鼠模型并进行毒理评价.方法 选取6～8周龄BALB/c雌鼠,经肺递送和滴鼻2种途径感染布鲁菌S19-CN,分别于第0、2、4、6、8周,观察并记录临床体征,采集样本,分别对脾脏和肺脏载菌量计数及抗体(血清)和细胞因子(血清和肺匀浆)进行检测.结果 与空白对照组比较,感染后,肺递送组、滴鼻组小鼠均未见病症;体质量无显著下降;脾重分别在感染后第2周、第4周达到峰值;肺载菌量均在第2周达到峰值,约107CFU/g;血清抗体均在感染后8周内维持较高水平,肺递送组和滴鼻组的血清和肺匀浆中均可检测到高浓度细胞因子IFN-γ、TNF-α,且肺递送组峰值高于滴鼻组,与空白对照比较差异有统计学意义(P均＜0.05).结论 本研究通过布鲁菌S19-CN液体气溶胶肺递送感染BALB/c小鼠,成功建立布鲁菌液体气溶胶感染小鼠模型.S19-CN引起BALB/c小鼠慢性感染,脾肿大明显,毒理作用显著;同时激发了较强的细胞免疫和体液免疫反应.%Objective To establish mouse models with pulmonary infection due to exposure to liquid aerosol of Brucella and assess its toxicological effects. Methods BALB/c female mice of 6 to 8 weeks old were exposed to Brucella abortus strain S19-CN (S19-CN) by intra-tracheal aerosol delivery route or intranasal instillation route. At 0, 2, 4, 6, 8 weeks post-infection, clinical signs were observed and recorded. Specimens were harvested to count bacteria burdens in lungs and spleens. The specific antibodies in serum and the cytokines in serum or lung homogenate were detected. Results Compared with the blank control group, no significant clinical sign or body weight decrease was found in mice of intra-tracheal aerosol delivery route group and intranasal instillation route group after infection. The spleen weight reached the peak at the second week and the fourth week post-infection respectively. The bacteria burdens in lung reached the peak at the second week, approximate to 107CFU/g; serum antibody maintained a high level within 8 weeks post-infection; High-concentration cytokines IFN-γ and TNF-α were detectable in serum and lung homogenate of rats in both intra-tracheal aerosol delivery route group and intranasal instillation route group, and the former was higher than the latter. The difference was statistical compared with blank control group (P ＜ 0.05). Conclusions Mouse model with pulmonary infection due to exposure to liquid aerosol of Brucella has been established successfully by intra-tracheal delivery of liquid aerosol of Brucella S19-CN in BALB/c mice. S19-CN causes chronic infection of BALB/c mice, induces significant splenomegaly and produces significant toxicological effects. Meanwhile, it elicits significant cellular and humoral immune response.
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