Qi Shi, QingQing Li, Changlin Wu, Shisi Ma, Chunlan Liang, Xiaoyi Fan, Jingxiang Zhong, Lian Liu
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引用次数: 0
Abstract
Background: Fungal keratitis (FK) is a kind of infectious keratopathy with a high rate of blindness worldwide. Deoxynivalenol (DON) has been proven to have multiple toxic effects on humans and animals.
Objectives: The aim of this study was to explore a possible pathogenic role of DON in FK.
Methods: We first made an animal model of FK in New Zealand white rabbits, and then attempted to detect DON in a culture medium in which Fusarium solani had been grown and also in the corneal tissue of the animal model of Fusarium solani keratitis. Next, a model of DON damage in human corneal epithelial cells (HCECs) was constructed to evaluate effects of DON on the activity, migration ability, cell cycle, and apoptosis in the HCECs. Then, putative the toxic damaging effects of DON on rabbit corneal epithelial cells and the impact of the repair cycle were studied. The expression levels of inflammatory factors in the corneas of the animal model and in the model of DON-damaged HCECs were measured.
Results: The Fusarium solani strain used in this study appeared to have the potential to produce DON, since DON was detected in the corneal tissue of rabbits which had been inoculated with this Fusarium solani strain. DON was found to alter the morphology of HCECs, to reduce the activity and to inhibit the proliferation and migration of HCECs. DON also induced the apoptosis and S-phase arrest of HCECs. In addition, DON was found to damage rabbit corneal epithelial cells, to prolong the corneal epithelial regeneration cycle, and to be associated with the upregulated expression of inflammatory factors in HCECs and rabbit corneas.
Conclusions: DON appears to have a toxic damaging effect on HCECs in FK, and to induce the expression of inflammatory factors, leading to the exacerbation of keratitis and the formation of new blood vessels. Future studies will explore the possibility of developing a test to detect DON in ophthalmic settings to aid the rapid diagnosis of FK, and to develop DON neutralizers and adsorbents which have the potential to improve keratocyte status, inhibit apoptosis, and alleviate inflammation, therein providing new thinking for therapy of clinical FK.
背景:真菌性角膜炎(FK真菌性角膜炎(FK)是一种感染性角膜病,在世界范围内致盲率很高。脱氧雪腐镰刀菌烯醇(DON)已被证实对人类和动物有多种毒性作用:本研究旨在探讨 DON 在 FK 中可能起到的致病作用:我们首先用新西兰白兔制作了一个 FK 动物模型,然后尝试在培养梭状芽孢杆菌的培养基和梭状芽孢杆菌角膜炎动物模型的角膜组织中检测 DON。接着,建立了一个 DON 对人角膜上皮细胞(HCECs)的损伤模型,以评估 DON 对 HCECs 的活性、迁移能力、细胞周期和细胞凋亡的影响。然后,研究了 DON 对兔角膜上皮细胞的推定毒性损伤作用以及对修复周期的影响。测量了动物模型角膜和 DON 损伤的 HCECs 模型角膜中炎症因子的表达水平:结果:本研究中使用的镰刀菌株似乎具有产生 DON 的潜力,因为在接种了该镰刀菌株的兔子角膜组织中检测到了 DON。研究发现,DON 能改变角膜细胞的形态,降低角膜细胞的活性,抑制角膜细胞的增殖和迁移。DON 还能诱导 HCECs 细胞凋亡和 S 期停滞。此外,研究还发现 DON 会损伤家兔角膜上皮细胞,延长角膜上皮再生周期,并与 HCECs 和家兔角膜中炎症因子的表达上调有关:结论:DON 似乎对 FK 中的 HCECs 有毒性破坏作用,并诱导炎症因子的表达,导致角膜炎恶化和新血管的形成。未来的研究将探索开发一种在眼科环境中检测 DON 的测试方法,以帮助快速诊断 FK,并开发 DON 中和剂和吸附剂,它们有可能改善角膜细胞状态、抑制细胞凋亡和缓解炎症,从而为临床 FK 的治疗提供新思路。
期刊介绍:
Mycopathologia is an official journal of the International Union of Microbiological Societies (IUMS). Mycopathologia was founded in 1938 with the mission to ‘diffuse the understanding of fungal diseases in man and animals among mycologists’. Many of the milestones discoveries in the field of medical mycology have been communicated through the pages of this journal. Mycopathologia covers a diverse, interdisciplinary range of topics that is unique in breadth and depth. The journal publishes peer-reviewed, original articles highlighting important developments concerning medically important fungi and fungal diseases. The journal highlights important developments in fungal systematics and taxonomy, laboratory diagnosis of fungal infections, antifungal drugs, clinical presentation and treatment, and epidemiology of fungal diseases globally. Timely opinion articles, mini-reviews, and other communications are usually invited at the discretion of the editorial board. Unique case reports highlighting unprecedented progress in the diagnosis and treatment of fungal infections, are published in every issue of the journal. MycopathologiaIMAGE is another regular feature for a brief clinical report of potential interest to a mixed audience of physicians and laboratory scientists. MycopathologiaGENOME is designed for the rapid publication of new genomes of human and animal pathogenic fungi using a checklist-based, standardized format.