| Background and ObjectiveEschar adheres to the deep partial-thickness wound causes a negativeeffect during burn wound healing. Due to the persistence of necrotic tissue(eschar) the local inflammation and infection become extensive andprofound, which may leads to a delayed healing. Therefore, early removalof eschar by using tangential excision or Chinese medicine has shown agreat therapeutic benefit in the deep partial-thickness burn.GM-CSF is synthesized and secreted by a variety of inflammatory cells(neutrophils and macrophages) and repair cells during wound healing. Inturn, GM-CSF chemoattracts inflammatory cells into the wound site andinduces productions of matrix metalloproteinases (MMPs). Previousstudies showed that proteolytic enzymes and MMPs play a major role indebridement of eschar of deep partial thickness burn. Thus, we hypothesizethat GM-CSF could deride the eschar of deep partial-thickness burn so thatcould speed up the process of wound healing.The propose of this study is to determine the effect of rhGM-CSF ondebridement of eschar in deep partial thickness scalding wound and themechanism for debridement of rhGM-CSF using animal experiments andclinical observations.Methods：1．Animal experiments： A total of70SD rats were scalded on the back using the method ofthermal-water burns at75°C for8s. A deep partial-thickness burn withdiameter of3cm per rat was created in all the rats. Scalded rats wererandomly divided into two groups（n=35）, namely, control group(C) andexperiment group(E). Control group(C) was treated with gel matrix(without rhGM-CSF), experiment group(E) was treated with rhGM-CSFgel（100μg/10g）. The wounds were treated with rhGM-CSF or gel matrixup to21day. Observations of the wounds were made by photograph atvarious time-points. In addition, the removal time of wound eschar in allanimals was recorded. The percentages of removal area in the woundswere calculated by image analysis software in various time-points. Thescalding wound specimens were obtained at different time points to observethe situation of morphology and repair in wound tissue with hematoxylinand eosin staining. Immunohistological staining was employed to analyzeinflammatory cells in wounds. ELISA was used to detect the expression ofElastase(NE), MMP-1, and MMP-9.2．Clinical observation：A total of58cases patients with deep partial thickness burn werecollected for this study from December2008to December2010in ourhospital. All patients were randomly divided into two groups, each groupwas treated topically with rhGM-CSF gel (experiment group) or gel matrix(control group). Dressing was changed at every other day. Theremoval-time and the percentage of removal-area of eschar were evaluatedat different time points during healing process.Results1．Animal experiments： 1．1．The removal-area percentage of eschar in the experiment group wassignificantly bigger than that in the control group from Day5post-injury(P <0.01). The average of removal-time of eschar in the experiment groupwas10.73±2.47d，which was much shorter than that in the control group14.26±2.65d (P <0.01). The time of wound healing in the experimentgroup was16.73±1.27d，which was significantly shorter than that in thecontrol group18.05±1.36d，(P <0.01);1．2．Pathological analyses showed that infiltration of inflammatory cells inwounds were higher in the experiment groups than those in control groupon day3and7post scalding, removal time of necrotic tissue in wounds inexperiment group much shorter than that in the control group.1．3．The NE levels in two groups after injury were significantly increasedfrom day3, reached the peak at day7post-injury. The levels of NEdecreased gradually to the pre-injury level at day14. The levels of NE inexperimental group were significantly higher than that in the control groupfrom day3to7after injury (P <0.01). The protein levels of MMP-1andMMP-9in two groups reached the peak at day7after injury, then decreasedgradually to the pre-injury level at day14. The levels of MMP-1andMMP-9protein in experimental group were significantly higher thancontrol group (P <0.01) from day3and10after injury.2．Clinical Study:Compared to that in the control group (14.13±3.34days), the time forcompleted removal eschar in the experiment group (7.71±2.76days) wasdramatically shorter（P<0.01). The total areas for eschar removal in theexperiment group were34.30±10.40，82.20±17.50，and98.36±4.46at day2,6, and10, respectively. It was significantly higher than that in thecontrol at the same time-points (11.03±4.47,40.69±11.56，and68.88±9.76， P<0.01). Furthermore, the time of wound healing in the experiment groupwas18.41±2.47days, which was much shorter than that in the controlgroup (23.58±3.35days, P <0.01).Conclusion:Animal experiments and clinical observations suggest that rhGM-CSFgel may promote debridement and wound healing in deep partial thicknessscalding,the mechanism of which may be associated with increaseinflammatory cells and acceleration of neovascularization in early woundand upregulation of expression of the enzyme activity. |
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