Expression of MMP-2and MMP-9in Local" Re-stimulated" Wound after Trauma
|Keywords||trauma immune response inflammatorycell inflammatory cytokines|
Background and objectiveClinically, surgical treatments, especially with tension suturing on subacute or chronicwounds that were more than6hours post-injury, likely to cause redness, swelling evenhistolysis around the stitches. It’s long been thought that due to wound infection, whichresult in delayed wound healing, higher medical expenses or medical disputes. However,by thoroughly cleaning and sterilizing above-mentioned wounds or even combined withantibiotics, those wound inflammation responses could not be eliminated. Basically, alarge number of inflammatory cells get together into wound and secrete abundantinflammatory mediator instantly after injury, assist wound healing. The quantity oflocal inflammatory mediator will gradually decrease if wound heals in time. Otherwise,the levels will stay high and continue with wound healing. On this basis, followed byanother negative stimulus such as re-injury, tension, foreign bodies, or microbes, theinflammatory cells around wounds will response much faster and stronger compare tothe first hit, this is called wound hyper-inflammatory response, which often causeredness, swelling or histolysis around the wound. Studies showed that theover-expression of MMP-2/MMP-9of tissue could degrade extracellular matrix andbasement membrane and then gave rise to tissue dissolution. In this study, weinvestigated the MMP-2/MMP-9variations on wounds which bear hyper-inflammatoryresponse.MethodsSD rat with full-thickness skin wound on the back was used as an experimental model.Wounds on ninety-six rats were divided into four groups as follow: a. suture group,wounds were made on the rats with size of0.5cm×4cm and were sealed on threedays post-injury with4-0non-injury thread or0-0silk thread (n=24); b. control group one, the same size of wounds were made and were instantly sutured after injury (n=24);c. high tension group, wounds were created on the rats with1.5cm×4cm size andwere closed on three days post-injury with4-0non-injury thread or0-0silk thread (n=24); d. control group one, the same size of wounds were made and were instantlysutured after injury (n=24). Animals were raised individually after treatments. On day2and4, HE staining and ELISA were applied to evaluate wound inflammation and thevariation of MMP-2/MMP-9；localization and expression of MMP-2/MMP-9wereanalyzed by IHC.Results1. General observation, rats in experimental groups were in poorer mental state，aswell as less activities.2. The expressions of MMP-2/MMP-9in experimental groups were significantlyhigher than control group (P <0.01). In experimental groups, wounds treatedwith0-0silk thread have greater MMP-2/MMP-9expressions than treated with4-0non-injury group (P <0.01); MMP-2/MMP-9expressions in high-tensiongroup (1.5cm×4cm) were significantly higher than low-tension groups(0.5cm×4cm)(P <0.01); The levels of MMP-2/MMP-9were increased alongwith time, but there was no significance (P>0.05).3. MMP-2/MMP-9barely express in normal skin; after injury, MMP-2chieflylocalize in polymorphoneuclear cells like fibroblasts in basement membrane anddermal epidermis, inflammatory cells around hair follicles; MMP-9mostlyexpress in cytoplasm, a little in cell nucleus or extracellular, some was foundinside epithelial cells, mainly distribute in inflammatory cells.4. HE staining showed that obvious vessel expand and much more inflammatorycells were found in experimental groups compared to control group,inflammatory cells even infiltrated into muscles for some specimen.Conclusions For sub-acute wound, second-hit factors like foreign body and tensioncould induce high MMP-2/MMP-9expression in local immune cells which can lead to hyper-inflammatory response like redness, swelling or tissue dissolve, and consequently,delay wound healing.