| Objective: For the feasibility study of a nude (athymic) mouse model for the study of burn wound healing and hypertrophic scar(HS) forming. To explore the effect of MMP-1, TIMP-1, and TGF-β1 on burn wound healing and HS forming using this model.Methods: Normal human full-thickness skin grafts were transplanted to the back of these nude (athymic) mice, and after about 15 days, 95% of these grafts would take. Heated copper stick was used to make deep Ⅱ degree burn wounds in the middle of these grafts. The range of post-injury samples included post-burn hour 12, days 2, 3, 5, 7, 15, 28, and mouths 3, 5. During the process of burn wound healing and scar forming, we recorded the gross appearance changes and harvested these full-thickness graft specimens. Every specimen was cut into two parts of An and Bn, and then we got two groups of specimens of group A and group B. Specimens of group A were used for study of microscopic tissue structure by HE and VG staining, and specimens of group B were used for the detection of expression of MMP-1, TIMP-1, and TGF-β1 by immunohistochemistry examination. Results: 1. Similar changes could be seen in this model as in the human body during the process of burn wound healing and scar forming. And hyperplasia of the scars could be seen with a peak in about 3 mouths, and softening and contraction in about 5 mouths. 2. Immunoreactive MMP-1 was first noted both in the dermis and the overlying eschar by day 2 after injury, and became more prominent from day 3 to day 15, and then decreased rapidly. Immunostaining for MMP-1 was markedly increased at the eschar-dermis interface, the epidermal-dermal junctions at the wound margins, the surviving epidermal appendages, and around blood vessels. Immunoreactive TIMP-1 was also detected by day 2 both in the dermis and the overlying eschar but rapidly assumed the same interface pattern as described for MMP-1. Immunostaining of TIMP-1 was irregular and discrepant at these interfaces and surviving epidermal appendages, but was obvious about vascular structures. ImmunoreactiveTGF-β1 could be seen by hour 12 and kept evident through the process of wound healing and scar forming. Immunostaining for TGF-β1 was distributed not only in the epidermis and dermis but also at these interfaces, surviving epidermal appendages, and around vascular structures.Conclusion: 1. Using this nude (athymic) mouse model, we studied the whole process of burn wound healing and HS forming. And such an in vivo model offered many possibilities lacking in the previous in vitro model. 2. The balance between MMP-1 and TIMP-1 during the inflammation and granulation phases might be important for the regulation of collagen proteins degradation, the migration and proliferation of blood vessel endothelium, and the dilatation of blood vessels. Within the remodeling phase, the inhibition of MMP-1 by TIMP-1 and the decrease of collagen degradation might be important for HS forming. The widespread and long-term expression of TGF-β1 during the process of burn wound healing and HS forming not only reveals its comprehensive function but also is coincident with its role in the inhibition of MMP-1 and stimulation of TIMP-1. 3. The striking immunolocalization of MMP-1, TIMP-1, and TGF-β1 to epithelial-dermal, eschar-dermal, and vascular-dermal interfaces suggested that they might play a particularly significant role at boundary regions marked by connective tissue fluidity.
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