吲哚胺2,3双加氧酶在系统性近平滑念珠菌感染小鼠中的作用

The Role of Indoleamine 2,3-dioxygenase in Candida Parapsilosis Systemic Infectet Mice

目的 观察吲哚胺2,3双加氧酶（IDO）在系统性近平滑念珠菌（CP）感染小鼠中的作用.方法 SPF级雌性ICR小鼠分为3组,模型组和抑制组小鼠尾静脉接种CP建立系统性近平滑念珠菌感染小鼠模型,对照组小鼠接种生理盐水.抑制组在接种CP当日经口给IDO抑制剂1甲基色氨酸（1-MT）,连续给药7d,模型组和对照组小鼠给生理盐水.分别在接菌后3d、6d和9d每组小鼠施行安死术5只,采集肾脏,进行IDO、炎症相关细胞因子检测,载菌量测定和组织病理学观察.结果 小鼠感染CP后肾组织IDO相对表达量升高,给予1-MT后IDO相对表达量下降;模型组肾脏IFN-γ、TNF-α、IL-6、IL-1β表达水平上调,抑制组除IFN-γ、TNF-α、IL-6和IL-1β表达水平上调外,接种CP后6d肾脏IL-17表达水平显著升高;载菌量结果显示,与模型组比较,接菌后6d抑制组肾脏载菌量显著高于模型组;病理观察结果显示,抑制组肾脏真菌感染病灶数量增多,组织破坏严重.结论 小鼠感染CP后肾组织IDO相对表达量升高,给予IDO抑制剂1-MT后肾组织IL-17表达水平升高,促进了慢性炎症,影响了真菌清除.

Objective To investigate the role of indoleamine 2,3-dioxygenase （IDO） in mice model of candida parapsilosis（CP） systemic infection. Methods The female ICR mice （SPF） were randomly divided into three groups, Group A and Group B were infected with CP by tail vein injection after immunosuppression, control group were injected physiological saline by tail vein injection. Group B were given methyl tryptophan （1-MT） by oral gavage, which is the inhibitor of IDO, each a day from 0 day to 7 days after infection. While group A and control group were given physiological saline by oral gavage. Five mice were euthanatized at 3, 6, 9 days after infection and the kidney tissues were collected and examined by the expression of IDO and inflammation related cytokines, fungal burden, and histology. Results After infection CP, the level of IDO in Group A was increased, while the IDO level was went down in group B. The level of IFN-7, NF-γ, IL-6 and IL- 1βin kidney was increased both in group A and group B comparing with control group. At 6 days after infection, the level of IL-17 in kidney in group B was increased significantly comparing with that of group A and control group. At 6 days after infection, the level of fungal burden in group B were higher than that of group A. More fungal infection focus and tissue destruction were seen in the kidneys under the microscope in group B. Conclusion The expres- sion level of IDO was increased in the mice model of CP systemic infection. When the inhibitor of IDO were given to the CP mice, the level of IL-17 in kidney was increased, which might promote chronic inflammation and inhibit the clearing of fungi.