Overcash R G, Lindsey J R, Cassel G H, Baker H J
Am J Pathol. 1976 Jan;82(1):171-90.
Hexamethylphosphoramide (HMPA) was given orally (100 mg/kg/day) to: a) conventional rats of Sprague-Dawley and Long-Evans substrains known to have indigenous Mycoplasma pulmonis infection, b) uninfected pathogen-free (PF) Fischer rats, and c) PF and axenic Fischer rats inoculated intranasally with M. pulmonis strains having a wide range of virulence. Treated rats infected with virulent M. pulmonis, either naturally or experimentally, developed severe clinical signs of murine respiratory mycoplasmosis (MRM) with mortalities of 25 to 60% compared to relatively mild MRM and no deaths in untreated, infected controls. Deaths were attributed to unusually severe lung lesions of MRM (extreme neutrophilic exudation into major bronchi and bronchiectasis) with ulceration of respiratory mucosa and hemorrhage. Rhinitis also was increased in severity by HMPA in conventional rats, but not in experimentally infected PF or axenic rats. Severity of otitis media and tracheitis was not affected by HMPA. Incidence of lesions of MRM was unchanged except for increased frequency of gross lung lesions. In the absence of M. pulmonis infection, HMPA treatment of rats caused thinning and microulceration of respiratory epithelium in major bronchi without inflammatory lung disease. Other effects induced by HMPA, with or without the infection, were destruction and fibrous replacement of olfactory epithelium, atrophy of testes, and reduced weight gains. It was concluded that HMPA markedly enhances both rate of progression and severity of the pneumonia while inconsistently potentiating the rhinitis of MRM in rats. Previous studies of HMPA are emphasized as an additional example in which the synergistic effects of an experimental chemical and an indigenous pathogen of laboratory rats have given misleading experimental results.
给以下几组大鼠口服六甲基磷酰胺（HMPA，100毫克/千克/天）：a）已知感染了肺支原体的Sprague-Dawley和Long-Evans亚系的普通大鼠；b）未感染的无特定病原体（PF）Fischer大鼠；c）经鼻接种了具有广泛毒力的肺支原体菌株的PF和无菌Fischer大鼠。与未治疗的感染对照相比，自然感染或实验感染强毒力肺支原体的治疗大鼠出现了严重的鼠呼吸道支原体病（MRM）临床症状，死亡率为25%至60%，而未治疗的感染对照的MRM相对较轻且无死亡。死亡归因于MRM异常严重的肺部病变（大量中性粒细胞渗出到主支气管和支气管扩张），伴有呼吸道黏膜溃疡和出血。HMPA还使普通大鼠的鼻炎严重程度增加，但在实验感染的PF或无菌大鼠中未增加。HMPA对中耳炎和气管炎的严重程度没有影响。除了肺部大体病变频率增加外，MRM病变的发生率没有变化。在没有肺支原体感染的情况下，HMPA处理大鼠会导致主支气管呼吸上皮变薄和微溃疡，但无炎症性肺病。无论有无感染，HMPA诱导的其他效应包括嗅觉上皮的破坏和纤维替代、睾丸萎缩以及体重增加减少。得出的结论是，HMPA显著提高了肺炎的进展速度和严重程度，同时不一致地增强了大鼠MRM的鼻炎。强调之前对HMPA的研究是另一个例子：实验化学品与实验大鼠的固有病原体的协同作用给出了误导性的实验结果。
