Keller Christopher E, Elliott Thomas B, Bentzel David E, Mog Steven R, Shoemaker Michael O, Knudson Gregory B
Center of Laboratory Animal Medicine, Department of Preventive Medicine and Biometrics, Uniformed Services University of the Health Sciences, 4301 Jones Bridge Road, Bethesda, Maryland 20814-4799, USA.
Comp Med. 2003 Aug;53(4):397-403.
Bacteria such as Klebsiella pneumoniae can invade and colonize an immunocompromised host and complicate clinical recovery. In the study reported here, an experimental model of induced pneumonia was developed in 60Co gamma-photon-irradiated mice for the purpose of evaluating efficacy of therapeutic agents. The model was characterized by use of probit analysis of bacterial dose, and microbiologic, and histopathologic results. Bacterial colony-forming-unit (CFU) values producing 50% mortality within 30 days (LD50/30) and their 95% confidence intervals were 4.0 x 10(4) [1.7 x 10(4) - 8.9 x 10(4)] for 0-Gray (Gy)-irradiated mice, 1.9 x 10(4) [7.0 x 10(3) - 4.8 x 10(4)] for 5-Gy-irradiated mice, and 1.0 x 10(3) [2.8 x 10(2) - 3.3 x 10(3)] for 7-Gy-irradiated mice. Probit regression line fits calculated by use of an iterative, weighted least-squares fit, were used to assess a dose-modifying factor (DMF). The DMFs for mortality, compared with that for the 0-Gy dose, with their 95% confidence intervals, were 2.2 [0.63 - 7.7] for the 5-Gy and 38.9 [9.6 -165.0] for 7-Gy doses. The 5-Gy probit line did not significantly differ (P = 0.21) from the 0-Gy probit line (dose ratios did not significantly differ from 1), whereas the 7-Gy probit line differed significantly from the 0-Gy probit line (P < 0.001). These results demonstrate that 7-Gy 60Co gamma-photon radiation in combination with intratracheal K. pneumoniae challenge induces a valid pulmonary infection model in immunocompromised female B6D2F1/J mice.
肺炎克雷伯菌等细菌可侵袭免疫功能低下的宿主并在其体内定植，使临床康复过程复杂化。在本研究中，为评估治疗药物的疗效，在经60钴γ光子辐照的小鼠中建立了诱导性肺炎实验模型。该模型的特点是利用细菌剂量的概率分析以及微生物学和组织病理学结果。在30天内产生50%死亡率的细菌菌落形成单位（CFU）值（LD50/30）及其95%置信区间，对于未辐照（0戈瑞，Gy）的小鼠为4.0×10⁴ [1.7×10⁴ - 8.9×10⁴]，对于5 Gy辐照的小鼠为1.9×10⁴ [7.0×10³ - 4.8×10⁴]，对于7 Gy辐照的小鼠为1.0×10³ [2.8×10² - 3.3×10³]。使用迭代加权最小二乘法拟合计算得到的概率回归直线来评估剂量修正因子（DMF）。与0 Gy剂量相比，5 Gy和7 Gy剂量死亡率的DMF及其95%置信区间分别为2.2 [0.63 - 7.7]和38.9 [9.6 - 165.0]。5 Gy的概率直线与0 Gy的概率直线无显著差异（P = 0.21）（剂量比与1无显著差异），而7 Gy的概率直线与0 Gy的概率直线有显著差异（P < 0.001）。这些结果表明，7 Gy的60钴γ光子辐射联合气管内肺炎克雷伯菌攻击可在免疫功能低下的雌性B6D2F1/J小鼠中诱导出有效的肺部感染模型。
