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Abstract Title:Perillaldehyde Ameliorates Aspergillus fumigatus Keratitis by Activating the Nrf2/HO-1 Signaling Pathway and Inhibiting dectin-1介导的炎症。
摘要来源:
投资Ophthalmol Vis Sci。 2020年6月3日; 61(6):51。 PMID: 32579678“> 32579678 Hu, Lingwen Gu, Guoqiang Zhu, Guiqiu Zhao, Jing Lin
Article Affiliation:Yiqun Fan
Abstract:Purpose: The purpose of this study was to investigate the therapeutic effect of perillaldehyde (PAE) on Aspergillus Fumigatus(A。fumigatus)角膜炎。
方法: 人类角膜上皮细胞(HCEC)是预处理的用PAE ED并用烟曲霉刺激。 C57BL/6小鼠被烟曲霉感染,并在感染后1天用或不使用PAE治疗。使用临床评分,PCR,ELISA和Western印迹来检测促炎性介质,树突状细胞相关的C型凝集素-1(dectin-1),核因子(红细胞衍生的2),如2(NRF2)和血红素氧酶(HEME氧酶(HO-1))。通过免疫荧光观察到用PAE预处理的HCEC中的NRF2表达。通过使用PAE处理后,通过免疫荧光染色观察到NIMP-R14蛋白表达和在小鼠角膜中的定位。 Corneal colony counting, time-kill tests, and mycelial transformation inhibition tests were used to evaluate the antifungal effect of PAE.
Results: C57BL/6 mice treated with PAE at 1 day after infection had a lower clinical score and decreased IL-1β, TNF-α, IL-6,Dectin-1和MPO水平。 PAE处理大大降低ED中性粒细胞募集到角膜基质。与经DMSO处理的组相比,PAE处理显着降低了HCEC中促炎细胞因子和dectin-1的mRNA和蛋白质水平。烟曲霉刺激前的PAE预处理显然升高了NRF2/HO-1轴成分的mRNA和蛋白质水平。在感染前用PAE预处理的HCEC显示在存在Brusatol(BT; NRF2抑制剂)或ZNPP(HO-1抑制剂)的情况下抑制炎症的能力较弱。 PAE treatmentsignificantly reduced the fungal load of C57BL/6 mouse corneas and inhibited fungal growth in vitro.
Conclusions: These data proved that PAE may ameliorate A. fumigatus keratitis by activating the Nrf2/HO-1 signaling pathway and inhibiting the Dectin-1介导的炎症反应和中性粒细胞募集。此外,PAE在A. fumigatus上发挥直接的杀真菌活性。