CRAMP诱导自噬提高烟曲霉角膜炎中巨噬细胞的杀真菌能力  

CRAMP Inducing Autophagy to Improve the Fungicidal Ability of Macrophages during Aspergillus fumigatus Keratitis

作　　者：侯晓晨 彭旭东[1] 林静[1] 

机构地区：[1]青岛大学附属医院眼科,山东 青岛

出　　处：《临床医学进展》2023年第3期4335-4343,共9页Advances in Clinical Medicine

摘　　要：CRAMP是一种能够抑制多种真菌生长的抗微生物肽,据报道CRAMP在细菌感染中能够调控巨噬细胞。本文对小鼠烟曲霉菌性角膜炎中CRAMP的治疗效果及对巨噬细胞的调控展开研究。方法:体内实验通过建立小鼠烟曲霉菌角膜炎模型,比较CRAMP或PBS处理组在裂隙灯照片、临床评分以及真菌负荷方面的差异。体外实验通过流式细胞技术分析CRAMP对巨噬细胞吞噬、杀灭细胞内杀真菌力的影响。RT-PCR和免疫蛋白印迹法检测巨噬细胞自噬相关基因和蛋白的表达,如LAMP-3、Beclin-1。结果:在烟曲霉角膜炎期间,CRAMP减少了小鼠角膜的真菌负荷并降低了角膜的临床评分。虽然CRAMP对烟曲霉感染巨噬细胞的吞噬作用无显著影响,但可显著加速巨噬细胞对细胞内真菌的清除。进一步的机制研究表明,CRAMP可上调LAMP-3和Beclin-1的表达,并通过诱导自噬提高巨噬细胞胞内杀真菌能力。结论:CRAMP可诱导自噬提高巨噬细胞的杀真菌能力,改善小鼠烟曲霉角膜炎预后。CRAMP is an antimicrobial peptide that inhibits the growth of a variety of fungi and has been re-ported to modulate macrophages in bacterial infections. In this paper, the therapeutic effect of CRAMP on Aspergillus fumigatus keratitis in mice and the regulation of macrophage were studied. Methods: In vivo, mice models with Aspergillus fumigatus keratitis were established to compare the statistic differences in slit-lamp photographs, clinical scores, and fungal loads between the CRAMP-treated or PBS-treated groups. In vitro, the effects of CRAMP on the phagocytosis and intra-cellular fungicidal ability of macrophages were analyzed by flow cytometry. RT-PCR and Western blot were used to detect the expression of autophagy related genes and proteins of macrophages, such as LAMP-3 and Beclin-1. Results: During Aspergillus fumigatus keratitis, CRAMP reduced fun-gal loads of mice corneas and lowered clinical scores. Although CRAMP had no significant effect on the phagocytosis of macrophages infected with Aspergillus fumigatus, it could significantly acceler-ate the intracellular fungal clearance by macrophages. Further mechanism studies showed that CRAMP could up-regulate the expression of LAMP-3 and Beclin-1, and elevate the intracellular fun-gicidal ability of macrophages by inducing autophagy. Conclusion: CRAMP can induce autophagy to elevate the fungicidal ability of macrophages and improve the prognosis of Aspergillus fumigatus keratitis in mice.

关 键 词：CRAMP 烟曲霉菌 巨噬细胞 自噬 杀真菌力 

分 类 号：R28[医药卫生—中药学]