中文摘要：

目的探讨超声雾化吸入新生隐球菌引起免疫抑制小鼠发生感染的可行性。方法 24只Balb/c小鼠随机分成2组,环磷酰胺（CTX）组12只腹腔内注射环磷酰胺再超声雾化吸入新生隐球菌,对照组12只直接吸人新生隐球菌。观察小鼠一般状况（食欲、体质量和行为等）和白细胞数目改变;感染3 d和7 d后处死小鼠,取外周血及肺、脑组织匀浆作真菌计数;肺组织切片染色作病理学观察。结果环磷酰胺注射后小鼠食欲差,体质量下降,注射后第4天白细胞数与对照组相比明显降低（2.77±0.45 vs8.26±0.56,P〈0.05）。CTX组小鼠在感染后3 d和7 d肺组织真菌负荷明显增高,肺组织菌落形成单位（CFU）分别为271.67±122.22和41.67±0.28,高于正常对照组的（P〈0.05）;CTX组小鼠感染后3 d和7 d外周血中可检出新生隐球菌,CFU分别为10.17±5.42和9.17±6.34,而对照组外周血在感染后3 d和7 d未培养出新生隐球菌;CTX组小鼠感染3 d和7 d后脑组织CFU分别为6.83±4.92和11.00±5.44,对照组脑组织未培养出新生隐球菌。肺组织病理切片可见免疫抑制小鼠感染后正常肺泡结构消失,肺泡壁增厚,炎性浸润明显,肺内可见新生隐球菌孢子。结论免疫抑制小鼠超声雾化吸入新生隐球菌后,肺组织真菌负荷增多并有明显炎性病变,在外周血和脑组织中可检出隐球菌。

英文摘要：

Objective To explore the feasibility of inducing fungal infection by Cryptococcus neoformans aerosol inhalation in immunosuppressed Balb/c mice.Methods Twenty-four Balb/c mice were randomized into cyclophosphamide（CTX） group and control group（n=12）.The mice in CTX group were subject to inhalation of Cryptococcus neoformans aerosol prepared using a ultrasonic nebulizer 4 days after intraperitoneal CTX injection,and the control mice received the inhalation only.The leukocyte count and changes in appetite,body weight,and behaviors of the mice were observed after the treatments.On days 3 and 7 after the inoculation,the mice were sacrificed to analyze the fungal counts in brain and lung tissue homogenates and examine the pulmonary pathologies.Results CTX injection caused lowered appetite and body weight loss in the mice,and significantly reduced the leukocyte counts（2.77±0.45 vs 8.26±0.56,P〈0.05）.At days 3 and 7 after inoculation,the Cryptococci load in the lungs increased obviously in CTX group with a colony-forming unit（CFU） of the lungs of 271.67±122.22 and 41.67±0.28,respectively,significantly higher than that in the control group（60.00±43.36 and 3.00±5.30,respectively,P〈0.05）.In CTX group,the CFU was 10.17±5.42 and 9.17±6.34 in the peripheral blood and 6.83±4.92 and 11.00±5.44 in the brain tissue at days 3 and 7,respectively,whereas no Cryptococci was detected in the peripheral blood or in the brain tissue in the control group. Pathological examination of the lungs revealed destruction of normal alveolar structure in CTX group,with numerous infiltrating inflammatory cells and visible yeast.Conclusion Inhalation of Cryptococcus neoformans aerosol can cause fungal infection in the lungs of immunosuppressed Balb/c mice.