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维生素 D3 联合氟康唑在小鼠模型中对阴道念珠菌病的预防和治疗作用。

Prophylactic and Therapeutic Role of Vitamin D3 in Combination with Fluconazole Against Vaginal Candidiasis in a Murine Model.

机构信息

Department of Medical Laboratories, College of Applied Medical Sciences, Qassim University, Buraydah-51452, Saudi Arabia.

出版信息

Curr Pharm Biotechnol. 2021;22(13):1812-1820. doi: 10.2174/1389201022666210218193445.

DOI:10.2174/1389201022666210218193445
PMID:33602072
Abstract

OBJECTIVE

In the present study, we assessed the adjunct effect of vitamin D3 in combination with Fluconazole (FLZ) against Vulvovaginal Candidiasis (VVC) in mice.

METHODS

Prophylactic effect was assessed by pretreating mice with vitamin D3 before exposure of mice with 2 X 10 CFUs of Candida albicans followed by treatment with FLZ. To determine the combined therapeutic efficacy, C. albicans infected mice were treated with a combination of vitamin D3 (10 μg/kg) and FLZ (10 and 20 mg/kg). The efficacy of the treatment was assessed by analyzing the fungal load and blood cell count. Moreover, the levels of inflammatory cytokines, including IL- 1β, IL-17 and TNF-α, were analyzed in the vaginal tissues. The histological analysis of the vaginal tissue from the untreated and treated mice was performed to assess the efficacy of the treatment.

RESULTS

Prophylactic treatment with vitamin D3 (10 and 20 μg/kg) significantly increased the therapeutic effect of FLZ against VVC. In a therapeutic experiment, mice in the infected control group showed the highest vaginal fungal load of 83627 ± 10058 CFUs. Treatment with FLZ at a dose of 10 mg/kg reduced fungal load to 55523 ± 14823 CFUs, whereas the mice treated with a combination of vitamin D3 and FLZ (10 mg/kg) had the fungal burden of 12156 ± 3219. Similarly, treatment with FLZ (20 mg/kg) reduced fungal load to 36394 ± 5648 CFUs, whereas the addition of vitamin D3 to FLZ (20 mg/kg) further reduced the fungal burden to 2179 ± 1188. The leukocyte numbers in the infected mice increased to 9802 ± 505 as compared to 5152 ± 778 in normal control mice. Whereas, a combination of vitamin D3 with FLZ (10 and 20 mg/kg) reduced leukocyte numbers to 7284 ± 607 and 5739 ± 1126. The histological analysis data revealed epithelial necrosis, shedding and ulceration in the vaginal wall. Treatment with FLZ or a combination of FLZ and vitamin D3 brought regenerative changes in the vaginal epithelium and lamina proparia.

CONCLUSION

The results of the present work recommend that the addition of vitamin D3 may be considered to increase the efficacy of FLZ against VVC.

摘要

目的

本研究评估了维生素 D3 联合氟康唑(FLZ)对阴道念珠菌病(VVC)的辅助作用。

方法

通过在 2X10CFUs 白念珠菌暴露前用维生素 D3 预处理小鼠,然后用 FLZ 治疗,评估预防效果。为了确定联合治疗效果,用维生素 D3(10μg/kg)和 FLZ(10 和 20mg/kg)联合治疗感染白念珠菌的小鼠。通过分析真菌负荷和血细胞计数来评估治疗效果。此外,还分析了阴道组织中炎症细胞因子 IL-1β、IL-17 和 TNF-α 的水平。对未经处理和处理的小鼠的阴道组织进行组织学分析,以评估治疗效果。

结果

预防性给予维生素 D3(10 和 20μg/kg)可显著增强 FLZ 对 VVC 的治疗效果。在治疗实验中,感染对照组的小鼠阴道真菌负荷最高,为 83627±10058CFUs。FLZ 10mg/kg 剂量治疗可使真菌负荷减少至 55523±14823CFUs,而维生素 D3 与 FLZ(10mg/kg)联合治疗组的真菌负担为 12156±3219CFUs。同样,FLZ(20mg/kg)治疗可使真菌负荷减少至 36394±5648CFUs,而维生素 D3 与 FLZ(20mg/kg)联合治疗可进一步将真菌负荷减少至 2179±1188CFUs。与正常对照组的 5152±778 相比,感染小鼠的白细胞数增加至 9802±505,而维生素 D3 与 FLZ(10 和 20mg/kg)联合治疗可将白细胞数减少至 7284±607 和 5739±1126。组织学分析数据显示阴道壁上皮坏死、脱落和溃疡。FLZ 或 FLZ 与维生素 D3 联合治疗可使阴道上皮和固有层再生。

结论

本研究结果表明,添加维生素 D3 可能有助于提高 FLZ 治疗 VVC 的疗效。

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