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 10⁶ 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.

目的：在本研究中，我们评估了维生素 D3 联合氟康唑 (FLZ) 对小鼠外阴阴道念珠菌病 (VVC) 的辅助作用。

方法：通过在小鼠接触 2 X 10 ⁶ CFU 的白色念珠菌之前用维生素 D3 预处理小鼠，然后用 FLZ 处理来评估预防效果。为了确定联合治疗效果，用维生素 D3 (10 μg/kg) 和 FLZ (10 和 20 mg/kg) 的组合治疗感染了白色念珠菌的小鼠。通过分析真菌负荷和血细胞计数来评估治疗的功效。此外，分析了阴道组织中炎性细胞因子的水平，包括 IL-1β、IL-17 和 TNF-α。对来自未治疗和治疗小鼠的阴道组织进行组织学分析以评估治疗效果。

结果：维生素 D3（10 和 20 μg/kg）的预防性治疗显着提高了 FLZ 对 VVC 的治疗效果。在治疗实验中，感染对照组的小鼠显示出最高的阴道真菌负荷为 83627 ± 10058 CFU。用 10 mg/kg 剂量的 FLZ 治疗将真菌负荷降低至 55523 ± 14823 CFU，而用维生素 D3 和 FLZ (10 mg/kg) 组合治疗的小鼠的真菌负荷为 12156 ± 3219。同样，治疗使用 FLZ (20 mg/kg) 将真菌负荷降低至 36394 ± 5648 CFU，而向 FLZ (20 mg/kg) 添加维生素 D3 进一步将真菌负荷降低至 2179 ± 1188。受感染小鼠的白细胞数量增加至9802 ± 505 与正常对照小鼠的 5152 ± 778 相比。然而，维生素 D3 与 FLZ（10 和 20 毫克/千克）的组合使白细胞数量减少到 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。用 FLZ 或 FLZ 和维生素 D3 的组合治疗使阴道上皮和固有层发生再生变化。

结论：目前的工作结果表明，可以考虑添加维生素 D3 以提高 FLZ 对 VVC 的疗效。