Boyd R L, Ramphal R, Rice R, Mangos J A
Infect Immun. 1983 Mar;39(3):1403-10. doi: 10.1128/iai.39.3.1403-1410.1983.
Colonization of the airways of rats by Pseudomonas aeruginosa was established by treating the animals with hexamethylphosphoramide (HMPA) and inoculating with P. aeruginosa. Male Sprague-Dawley rats were given tap water (controls) or HMPA in the drinking water at 2 or 4 mg/ml. The ciliated cells of the airway epithelium were denuded, and microulcerative lesions in the epithelium were induced in the HMPA-treated rats. After 2 weeks of treatment, the rats were inoculated by transoral intratracheal instillation with 5 X 10(7) CFU of P. aeruginosa obtained from a cystic fibrosis patient. Two weeks after inoculation, P. aeruginosa was cultured from the airways, and scanning and transmission electron microscopy showed bacilli adhering to or invading the injured airway epithelium. P. aeruginosa was present in tracheal and intrapulmonary tissue homogenates of 9% of the P. aeruginosa-inoculated control rats (n = 22) as compared with 61% of the 2-mg/ml (n = 18) and 65% of the 4-mg/ml (n = 20) HMPA-treated rats (P less than 0.05). No dose-response relationship was found between 2 and 4 mg of HMPA per ml and colonization. Contamination of 47% of all of the rats with Mycoplasma pulmonis, as indicated by a positive enzyme-linked immunosorbent assay for immunoglobulin G, had no discernible significant effect on colonization by P. aeruginosa. These results indicate that colonization of the rat airway by P. aeruginosa can be achieved experimentally by treating the animals with HMPA. This research supports the hypothesis that colonization by P. aeruginosa may occur in airways where the ciliated epithelium has been injured and epithelial lesions exist.
通过用六甲基磷酰胺（HMPA）处理大鼠并接种铜绿假单胞菌，建立了大鼠气道被铜绿假单胞菌定植的模型。将雄性Sprague-Dawley大鼠分为两组，一组给予自来水（对照组），另一组给予饮用水中浓度为2或4mg/ml的HMPA。HMPA处理的大鼠气道上皮的纤毛细胞脱落，上皮出现微溃疡性病变。处理2周后，经口气管内滴注从一名囊性纤维化患者分离得到的5×10⁷CFU铜绿假单胞菌。接种2周后，从气道培养出铜绿假单胞菌，扫描电镜和透射电镜显示杆菌附着或侵入受损的气道上皮。接种铜绿假单胞菌的对照组大鼠（n = 22）中，9%的大鼠气管和肺内组织匀浆中有铜绿假单胞菌，而2mg/ml组（n = 18）的大鼠中有61%，4mg/ml组（n = 20）的大鼠中有65%（P<0.05）。每毫升2至4mg的HMPA剂量与定植之间未发现剂量反应关系。酶联免疫吸附试验检测免疫球蛋白G呈阳性，表明所有大鼠中有47%感染了肺支原体，但这对铜绿假单胞菌的定植没有明显的显著影响。这些结果表明，通过用HMPA处理大鼠，可以在实验中实现铜绿假单胞菌在大鼠气道的定植。本研究支持这样的假说，即铜绿假单胞菌的定植可能发生在纤毛上皮受损且存在上皮病变的气道中。
