权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

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.

MMPs及其在创面愈合过程中的功能和调控尚不完全清楚。慢性创伤实验模型的缺乏是目前评价的主要问题。我们使用压疮组织评估MMPs的功能。在上皮边缘，MMP2和MMP9在基底层到颗粒层之间的上皮细胞中表达上调。压疮中部未见MMPs和TIMPs。随着上皮的形成，伤口成纤维细胞和伤口巨噬细胞表达MMP2、MMP9和TIMP2。为了建立动物模型，我们评估了慢性肾衰竭大鼠和肉桂小鼠的伤口愈合情况。慢性肾衰竭大鼠的切口创面和全层创面均未见延迟愈合现象。在肉桂小鼠中观察到伤口愈合的延迟。最后观察皮肤创面是否形成生物膜。在SD大鼠背部制造全厚或部分厚创面。将携带编码绿色荧光蛋白基因的铜绿假单胞菌（p.a uluginosa, PAO1）混悬液应用于受伤部位。取创面进行组织学和免疫组织化学处理。我们证实，在本实验模型中可以观察到铜绿假单胞菌在皮肤创面上形成生物膜，部分厚度创面适合观察生物膜的形成。同时，一个标准化的背侧缺血皮瓣被提起并缝合。皮瓣上有部分厚度创面。与非缺血对照组相比，缺血创面生物膜的形成程度明显减少。实验模型创面缺血不增加生物膜的形成。