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实验性镰刀菌性角膜炎角膜组织中的炎症和氧化应激:伏立康唑和表没食子儿茶素没食子酸酯局部治疗后的改善。

Inflammation and oxidative stress in corneal tissue in experimental keratitis due to Fusarium solani: Amelioration following topical therapy with voriconazole and epigallocatechin gallate.

机构信息

Department of Animal Science, School of Life Sciences, Bharathidasan University, Tiruchirappalli, Tamil Nadu, India.

Thomas Diagnostic and Research Centre, Tiruchirapalli, Tamil Nadu, India.

出版信息

Mycoses. 2018 Mar;61(3):159-171. doi: 10.1111/myc.12718. Epub 2017 Nov 16.

DOI:10.1111/myc.12718
PMID:29064157
Abstract

Combined antifungal and antioxidant therapy may help to reduce oxidative stress in fungal keratitis. Experimental Fusarium solani keratitis was induced by application of F. solani conidia to scarified cornea (right eye) of 16 rabbits (another four rabbits were negative controls [Group I]). Five days later, F. solani-infected animals began receiving hourly topical saline alone (Group II), voriconazole (10 mg/mL) alone (Group III), epigallocatechin gallate (EGCG, 10 mg/mL) alone (Group IV) or voriconazole and EGCG (Group V). Twenty days post-inoculation, corneal lesions were graded. After animal sacrifice, excised corneas underwent histopathological and microbiological investigations. Corneal tissue levels/activities of interleukin 1 beta (IL-1β) and tumour necrosis factor alpha (TNF-α) gene mRNA transcripts, matrix metalloproteinase (MMP) 2 and 9 proteins, malondialdehyde (MDA) and reduced glutathione (GSH), and superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx), were also measured. Clinical and histopathological scores (severity of corneal lesions; [P < .05]) and mean levels (P < .05) of IL-1β and TNF-α mRNA transcripts, MMP 2, MMP 9 and MDA were Group II > Groups IV and III > Groups V and I. Mean SOD, CAT, GPx and GSH levels (P < .05) were Group II < Groups IV and III < Groups V and I. Topical voriconazole with EGCG apparently reduces inflammation in experimental F. solani keratitis, as manifested by improved clinical, histological, microbiological and molecular parameters.

摘要

联合抗真菌和抗氧化治疗可能有助于减少真菌性角膜炎的氧化应激。通过将茄病镰刀菌孢子接种到划痕角膜(右眼)来诱导实验性茄病镰刀菌角膜炎(另外 4 只兔子为阴性对照[组 I])。 5 天后,茄病镰刀菌感染的动物开始接受单独的每小时局部生理盐水(组 II)、伏立康唑(10mg/mL)(组 III)、表没食子儿茶素没食子酸酯(EGCG,10mg/mL)(组 IV)或伏立康唑和 EGCG(组 V)。接种后 20 天,对角膜病变进行分级。动物牺牲后,切除的角膜进行组织病理学和微生物学检查。还测量了角膜组织中白细胞介素 1β(IL-1β)和肿瘤坏死因子α(TNF-α)基因 mRNA 转录物、基质金属蛋白酶(MMP)2 和 9 蛋白、丙二醛(MDA)和还原型谷胱甘肽(GSH)以及超氧化物歧化酶(SOD)、过氧化氢酶(CAT)和谷胱甘肽过氧化物酶(GPx)的水平/活性。临床和组织病理学评分(角膜病变严重程度;[P<.05])和平均水平(P<.05)的 IL-1β和 TNF-α mRNA 转录物、MMP 2、MMP 9 和 MDA 为组 II>组 IV 和 III>组 V 和 I。平均 SOD、CAT、GPx 和 GSH 水平(P<.05)为组 II<组 IV 和 III<组 V 和 I。局部伏立康唑联合 EGCG 可明显减轻实验性茄病镰刀菌角膜炎的炎症,表现为临床、组织学、微生物学和分子参数的改善。

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