Localization of MMP and TIMP on the chronic skin wounds and possible application of MMP inhibitor

MMP 和 TIMP 在慢性皮肤伤口上的定位以及 MMP 抑制剂的可能应用

基本信息

批准号：
17591871
负责人：
TACHI Masahiro
金额：
$ 2.18万
依托单位：
Tohoku University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2005
资助国家：
日本
起止时间：
2005 至 2006
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-17591871/
关键词：
MMP TIMP chronic wound biofilm 褥瘡 MMP阻害薬実験動物虚血皮弁

项目摘要

The functions and regulations of MMPs and MMPs on the wound healing process are not fully understood. The lack of experimental models for chronic wounds is the main problem for the evaluation. We evaluated the functions of MMPs using pressure ulcer tissues. At the edge of epithelization, MMP2 and MMP9 are upregulated in the epithelial cells between basal layer to granular layers. In the middle area of pressure ulcer, MMPs and TIMPs are not found. Along with epithelization, wound fibroblast and wound macrophage expressed MMP2 and MMP9 and TIMP2. For the development of animal model, we evaluated wound healing in the chronic renal failure rat and cinnamon mouse. Delay of wound healing of incisional wound and full thickness wound was not observed in the chronic renal failure rat. Delay in the wound healing was observed in cinnamon mouse. The final study was to observe whether biofilm formation occurs on skin wounds. Full or partial thickness wounds were created on the backs of SD rats. Suspensions of P.aeruginosa (PAO1 carrying the gene encoding the green fluorescent protein) was applied on the wounded area. Wounds were harvested and processed for histology and immunohistochemistry. The presence of biofilm were indicated Rhodamine-conjugated concanavalin A. We confirmed biofilm formation by P.aeruginosa on skin wounds can observe in this experimental model, and partial thickness wounds were proper for to observe biofilm formation. Also, a standardized dorsal ischemic flap was lifted and sutured. Partial thickness wounds were created on the flap. The extent of biofilm formation was significantly diminished on the surface of ischemic wound compared with non-ischemic control. Wound ischemia in the experimental model does not increase the formation of biofilms.

MMP和MMP在伤口愈合过程中的功能和法规尚不完全了解。缺乏慢性伤口的实验模型是评估的主要问题。我们使用压溃疡组织评估了MMP的功能。在上皮化的边缘，MMP2和MMP9在基础层之间的上皮细胞中上调。在压疮的中部，找不到MMP和TIMP。随着上皮化，伤口成纤维细胞和伤口巨噬细胞表达MMP2和MMP9和TIMP2。为了开发动物模型，我们评估了慢性肾衰竭大鼠和肉桂小鼠的伤口愈合。在慢性肾衰竭大鼠中未观察到切口伤口伤口愈合和全厚性伤口的延迟。在肉桂小鼠中观察到伤口愈合的延迟。最终的研究是观察生物膜是否发生在皮肤伤口上。在SD大鼠的背部产生了完全或部分厚的伤口。在受伤的区域施加了p.aeruginosa的悬浮液（携带编码绿色荧光蛋白的基因的PAO1）。收获伤口并处理以进行组织学和免疫组织化学。在这种实验模型中，可以观察到生物膜的存在。此外，提起并缝合了标准化的背缺血性皮瓣。在皮瓣上产生了部分厚度伤口。与非缺血对照相比，缺血性伤口表面的生物膜形成程度显着降低。实验模型中的伤口缺血不会增加生物膜的形成。