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小鼠模型中口腔念珠菌感染的光动力疗法

Photodynamic therapy of oral Candida infection in a mouse model.

作者信息

Freire Fernanda, Ferraresi Cleber, Jorge Antonio Olavo C, Hamblin Michael R

机构信息

Wellman Center for Photomedicine, Massachusetts General Hospital, Boston, MA, USA; Department of Biosciences and Oral Diagnosis, Institute of Science and Technology, Universidade Estadual Paulista (UNESP), São José dos Campos, São Paulo, Brazil.

Wellman Center for Photomedicine, Massachusetts General Hospital, Boston, MA, USA.

出版信息

J Photochem Photobiol B. 2016 Jun;159:161-8. doi: 10.1016/j.jphotobiol.2016.03.049. Epub 2016 Apr 1.

Abstract

Species of the fungal genus Candida, can cause oral candidiasis especially in immunosuppressed patients. Many studies have investigated the use of photodynamic therapy (PDT) to kill fungi in vitro, but this approach has seldom been reported in animal models of infection. This study investigated the effects of PDT on Candida albicans as biofilms grown in vitro and also in an immunosuppressed mouse model of oral candidiasis infection. We used a luciferase-expressing strain that allowed non-invasive monitoring of the infection by bioluminescence imaging. The phenothiazinium salts, methylene blue (MB) and new methylene blue (NMB) were used as photosensitizers (PS), combined or not with potassium iodide (KI), and red laser (660nm) at four different light doses (10J, 20J, 40J and 60J). The best in vitro log reduction of CFU/ml on biofilm grown cells was: MB plus KI with 40J (2.31 log; p<0.001); and NMB without KI with 60J (1.77 log; p<0.001). These conditions were chosen for treating the in vivo model of oral Candida infection. After 5days of treatment the disease was practically eradicated, especially using MB plus KI with 40J. This study suggests that KI can potentiate PDT of fungal infection using MB (but not NMB) and could be a promising new approach for the treatment of oral candidiasis.

摘要

念珠菌属真菌可引发口腔念珠菌病,尤其是在免疫抑制患者中。许多研究已对光动力疗法(PDT)在体外杀灭真菌的应用展开调查,但在感染动物模型中的相关报道却很少。本研究探究了PDT对白色念珠菌生物膜的影响,该生物膜分别在体外以及免疫抑制小鼠口腔念珠菌感染模型中生长。我们使用了一种表达荧光素酶的菌株,通过生物发光成像对感染进行非侵入性监测。吩噻嗪盐、亚甲蓝(MB)和新亚甲蓝(NMB)被用作光敏剂(PS),分别单独使用或与碘化钾(KI)联合使用,并采用四种不同光剂量(10J、20J、40J和60J)的红色激光(660nm)。在体外生长于生物膜上的细胞中,每毫升CFU的最佳对数减少量为:40J的MB加KI(2.31对数;p<0.001);以及60J的无KI的NMB(1.77对数;p<0.001)。这些条件被用于治疗口腔念珠菌感染的体内模型。治疗5天后,疾病几乎被根除,尤其是使用40J的MB加KI时。本研究表明,KI可增强使用MB(而非NMB)的真菌性感染的PDT效果,可能成为治疗口腔念珠菌病的一种有前景的新方法。

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本文引用的文献

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Global trends in the distribution of Candida species causing candidemia.全球引起念珠菌血症的念珠菌属物种分布趋势。
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Mechanisms of Candida biofilm drug resistance.念珠菌生物膜耐药机制。
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