Effect of 17-AAG combined with Caspofungin on invasive pulmonary aspergillosis in rats with neutrophil deficiency
ZHAN Xin1 WU Shiheng1 DENG Lin1 ZHANG Hongyue1 GAO Fusheng2▲
1.Clinical Medical School, Weifang Medical University, Shandong Province, Weifang 261000, China;
2.Department of Respiratory Medicine, Affiliated Hospital of Weifang Medical University, Shandong Province, Weifang 261000, China
Abstract：Objective To explore the effects of the combination of Hsp90 inhibitor 17-AAG (17-allyl-17-demethoxygeldanamycin) and Caspofungin (CAS) in the treatmemt of invasive aspergillosis (IPA) with neutrophil deficiency. Methods Forty male Wistar rats were divided into 4 groups, group A, group B, group C and group D, according to random number table method, with 10 rats in each group. Neutrophil deficiency models were made by intraperitoneal injection of Cyclophosphamide in four groups of rats, and then Aspergillus fumigatus spore suspension was inhaled through nose. Group A was fed normally and served as blank control. Group B and C were given CAS of 1 mg/kg and 17-AAG of 1 mg/kg respectively by intraperitoneal injection. Group D was given 17-AAG combined with CAS (the same usage and dosage) for 10 days. The survival status of rats was recorded. The serum galactomannan antigen (GM) was detected on the 3rd and 7th day after treatment, and the lung tissues were stained with GMS to observe the fungal load at the infected sites. Results Compared with group A, the survival rates of group B and group D were significantly increased (P < 0.01), and the average survival time of group D was longer than that of group B, but the difference was not statistically significant (P > 0.05). Compared with group A, there was no significant difference in GM values between the groups on the third day of treatment (P > 0.05). On the 7th day of treatment, the GM values of each treatment group were lower than those of group A (P < 0.01), while group D was lower than group B (P < 0.05). GMS staining of lung slices showed that the lesions of fungal infection decreased in all treatment groups, and the most significant reduction was found in group D. No lesions were found on the 15th day of treatment. Conclusion 17-AAG improves the efficacy of CAS in the treatment of IPA by inhibiting stress response.
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2019, Vol. 16 
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