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一种由 N-乙酰葡糖胺处理诱导的胃严重定植的新型小鼠念珠菌病模型及其基于胃部局部特征症状的评分系统。

A Novel Murine Candidiasis Model with Severe Colonization in the Stomach Induced by N-acetylglucosamine-treatment and Its Scoring System Based on Local Characteristic Stomach Symptoms.

作者信息

Ishijima Sanae A, Abe Shigeru

机构信息

Teikyo University Institute of Medical Mycology.

出版信息

Med Mycol J. 2015;56(4):E31-9. doi: 10.3314/mmj.56.E31.

Abstract

We developed a novel murine candidiasis model of the gastrointestinal tract using N-acetylglucosamine ( GlcNAc ) as a tool to aggravate symptoms. Forty-eight hours after intragastrically inoculating Candida albicans cells to immunosuppressed and GlcNAc-treated mice, vigorously accumulating patchy whitish plaques were observed on their inner stomach surface. Candida cells colonizing the plaques consisted of both yeast and mycelia, and were directly stained with Calcofluor White M2R. Aggravation of the candidiasis symptoms was dependent on GlcNAc concentration in drinking water, wherein administration of 50 mM GlcNAc not only severely worsened stomach symptoms, but also significantly increased Candida cell number in the stomach and small intestine. The aggravation effect of GlcNAc was enhanced by addition of sedative chemical chlorpromazine chloride after inoculation. In order to semi-quantitatively assess colonization by Candida in the stomach, we devised a new symptom scoring system that represents the extent of the patchy whitish plaques on the mucosal epithelium of the stomach. Histochemical analysis of Candida-infected tissues revealed not only a large amount of thick Candida mycelia invading mucosal epithelial stomach tissues but also infiltrating inflammatory cells. These results suggest that this murine gastrointestinal candidiasis model could serve as a useful tool for evaluating the protective activity of antifungal agents, probiotics, or functional foods against gastrointestinal candidiasis. Furthermore, from another point of view, this novel murine model could also be used to analyze the pathological mechanisms behind the translocation of C. albicans across intestinal barriers, which results in systemic Candida dissemination and infection.

摘要

我们利用N-乙酰葡糖胺(GlcNAc)作为加重症状的工具,开发了一种新型的小鼠胃肠道念珠菌病模型。在对免疫抑制且经GlcNAc处理的小鼠进行胃内接种白色念珠菌细胞48小时后,在其胃内表面观察到大量聚集的片状白色斑块。定殖于斑块中的念珠菌细胞由酵母和菌丝体组成,并用荧光增白剂M2R直接染色。念珠菌病症状的加重取决于饮用水中GlcNAc的浓度,其中给予50 mM GlcNAc不仅会严重恶化胃部症状,还会显著增加胃和小肠中的念珠菌细胞数量。接种后添加镇静化学物质氯丙嗪可增强GlcNAc的加重作用。为了半定量评估胃中念珠菌的定殖情况,我们设计了一种新的症状评分系统,该系统代表胃黏膜上皮上片状白色斑块的程度。对念珠菌感染组织的组织化学分析显示,不仅有大量粗大的念珠菌菌丝侵入胃黏膜上皮组织,还有炎性细胞浸润。这些结果表明,这种小鼠胃肠道念珠菌病模型可作为评估抗真菌剂、益生菌或功能性食品对胃肠道念珠菌病保护活性的有用工具。此外,从另一个角度来看,这种新型小鼠模型还可用于分析白色念珠菌跨肠道屏障移位背后的病理机制,这种移位会导致念珠菌在全身扩散和感染。

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