耐药白色念珠菌弥散性感染小鼠模型 z-bo 2020-12-23 301

　　OBJECTIVE: To establish a mouse model of diffuse infection of drug-resistant Candida albicans for the screening of new drugs.

　　Method: Clinical fluconazole-resistant Candida albicans CaR was injected intravenously into immunosuppressive ICR mice, and the model was evaluated by clinical symptoms, survival status, tissue load, histopathology, cytokine analysis, and drug treatment.

　　Results: CaR-infected mice died on the first day after vaccination. Compared with the clinical drug sensitive strain CaS-infected group, there was no significant difference in animal mortality during the 16-d observation period (CaR, 90.7%; CaS, 86.2%, P= 0.158), but it was observed that the early death of CaR group was faster than that of CaS group. On the fourth day of infection, Candida can be detected in different tissues, and it was found that compared with the CaS group, the amount of bacteria in the kidney and brain tissues was significantly different. The typical granulomas caused by fungi are the main histopathological features of kidney, brain and heart. Using flow cytometry to detect renal tissue cytokines, IL-1α, IL-6, TNF-α, IFN-γ and other cytokines changed significantly. Compared with the CaS group, IL-1α and IFN-γ were significantly increased, and TNF- Alpha dropped significantly. CaR and CaS infected mice were treated with fluconazole at 10 mg/kg, and the mortality rate was 83.3% and 37.5%, respectively, with significant differences.

　　Conclusion: This study successfully established a mouse model of drug-resistant Candida albicans diffuse infection, which is expected to become an important tool for the development of new anti-infective drugs.