巨噬细胞移动抑制因子及其拮抗剂ISO-1在病理性瘢痕发病机制中的作用  

Role of MIF and its antagonist ISO-1 in the pathogenesis of pathological scars

作　　者：梁大宁 柯昌能 

机构地区：[1]广东省深圳市龙华新区中心医院烧伤整形外科,518110

出　　处：《实用医学杂志》2017年第3期412-416,共5页The Journal of Practical Medicine

摘　　要：目的:探究巨噬细胞移动抑制因子(MIF)参与病理性瘢痕发病的具体机制,以及其拮抗剂ISO-1对病理性瘢痕来源成纤维细胞的影响。方法:收集正常皮肤、正常瘢痕以及病理性瘢痕标本,行HE以及免疫组化染色。利用组织块培养法分离培养人成纤维细胞,予以不同浓度ISO-1干预(0~100μmol/mL)。TUNEL染色检测细胞凋亡,Western blot以及RT-PCR检测成纤维细胞特异性蛋白以及PI3K/Akt/mTOR通路的表达情况。结果:MIF在增生性瘢痕、瘢痕疙瘩中表达强于正常瘢痕和正常皮肤。无干预组凋亡细胞较少,予以不同浓度ISO-1干预后,凋亡率逐渐上升。各组各时间点组间迁徙率比较差异均具有统计学意义(P<0.05)。随着干预浓度上升,Ⅰ型胶原蛋白、纤连蛋白以及结缔组织生长因子的蛋白和mRNA表达量均下降。活化PI3K以及活化Akt表达量随着ISO-1浓度增加而下降。结论:MIF在不同类型瘢痕组织中表达存在差异,ISO-1通过PI3K/Akt/mTOR通路抑制成纤维细胞生物学行为。Objective To explore the role of macrophage migration inhibitory factor （MIF） in the pathogen- esis of pathological scar and the effect of ISO- 1 on the behavior of scar fibroblasts. Methods Samples of normal skin, normal scar, and pathological scar were collected and detected by hematoxylin-eosin staining and immumohis- tochemical staining. Human fibroblasts were isolated from the samples and then divided into different groups with the intervention with ISO-1 （0 ~ 100 μ mol/mL）. Fibroblast proliferation was detected by Alamber dyeing and cell apoptosis was detected by TUNEL staining. Expressions of fibroblast specific proteins and PI3K/Akt/mTOR signal- ing pathways were detected by Western Blot and RT-PCR. Results The positive rates of MIF for hyperplastic scar and keloid were greater than those for normal sear and normal skin （P 〈 0.01）. Apoptotic cells occurred less in the group without intervention. The apoptotic rate increased gradually as the concentration of ISO- 1 increased. There were significant statistical differences in the migration rate among all the groups （P 〈 0.05）. As concentration of ISO-1 increased, the protein and gene expressions of type I collagen, FN and CTGF were decreased. Expressions of activated PI3K and Akt decreased as ISO-1 concentration increased. Conclusions The expression of MIF is different in different types of scar tissue. ISO-1 inhibits the biological behavior of fibroblasts derived from pathological scar through PI3K/Akt/mTOR pathways.

关 键 词：巨噬细胞移动抑制因子 病理性瘢痕 ISO-1 成纤维细胞 

分 类 号：R622[医药卫生—整形外科]