Abstract

In this study, we investigated the therapeutic efficacy of a combination of liposomal amphotericin B (Lip-Amp B) and Methylglyoxal (Lip-MG) against Candida albicans in the leukopoenic mice. The antifungal efficacy of Lip-Amp B or Lip-MG or a combination of Lip-Amp B and Lip-MG was evaluated by the analysis of the survival rate and the fungal load in the treated mice. The immune-stimulatory effect of Lip-MG on macrophages was evaluated by analysing the secretion of proinflammatory cytokines. C. albicans infected mice treated at the doses of 1 and 2 mg/kg of Lip-Amp B showed 20% and 50% survival rates, respectively. Whereas the mice treated with free Amp B at the same doses died within 40 days of treatment. Interestingly, C. albicans infected mice treated with a combination of Lip-Amp B and Lip-MG had 70% survival rate on day 40 postinfection. Moreover, treatment of macrophages with Lip-MG increased their fungicidal activity and the secretion of proinflammatory cytokines, including TNF-α and IL-1β. These findings suggested that co-treatment with Lip-Amp B and Lip-MG had a synergistic effect and could be effective against C. albicans in immunocompromised subjects.

摘要

在这项研究中，我们研究了脂质体两性霉素 B (Lip-Amp B) 和甲基乙二醛 (Lip-MG) 的组合对白细胞减少小鼠的白色念珠菌的治疗效果。Lip-Amp B 或 Lip-MG 或 Lip-Amp B 和 Lip-MG 的组合的抗真菌功效通过分析治疗小鼠的存活率和真菌负荷来评估。Lip-MG 对巨噬细胞的免疫刺激作用是通过分析促炎细胞因子的分泌来评估的。以 1 和 2 毫克/千克 Lip-Amp B 剂量处理的白色念珠菌感染小鼠分别显示 20% 和 50% 的存活率。而用相同剂量的游离 Amp B 治疗的小鼠在治疗后 40 天内死亡。有趣的是，白色念珠菌用 Lip-Amp B 和 Lip-MG 组合治疗的受感染小鼠在感染后第 40 天的存活率为 70%。此外，用 Lip-MG 处理巨噬细胞增加了它们的杀真菌活性和促炎细胞因子的分泌，包括 TNF-α 和 IL-1β。这些发现表明，与 Lip-Amp B 和 Lip-MG 共同治疗具有协同作用，并且可以有效对抗免疫功能低下受试者的白色念珠菌。