| ObjectiveHyperplastic scar is a common situation which appears from excessive repair of wound after being injured of the skin, thus, the prevention and treatment is a key research in the field of wound healing. In recent years, several studies have suggested that BTXA has a positive therapeutic effect, because it can enhance the apoptosis of the fibroblast and reduce the synthesis of collagen. Through establishing the model of rabbit ear hyperplastic scar on the ventral, injecting BTXA in the surface of the wound at the early stage, dynamic observation of the influence of BTXA on wound healing, scar formation and protein expression of the VEGF, cox-2,the Bcl-2and Bax, this report showed the effect of BTXA for prevention and treatment of the early HS, further discussed the mechanism of BTXA on the prevention and treatment of hyperplastic scar, provided theoretical basis for the prevention of the scar and expands the application area of BTXA.Methods①Sixteen healthy New Zealand white rabbit were chosen as experimental animals. They are2.5±0.2kg, including healthy whole ear tissues, regardless of gender. On the each side of the rabbit ear, cut a diameter of one centimeter full-thickness skin to create wounds at the proximal, middle and distal end, with an interval of one centimeter. According to the different drugs, these rabbits were divided into experimental groups and control groups:the left ears were BTXA experimental group (group T); the right ears were normal saline control group (group S). Each group contains48wounds. The rest of the8rabbits were normal ear skin blank group (group B).②Group T were given subcutaneous injection of0.12ml (3u) botulinum toxin A in each wound while group S were given subcutaneous injection of0.12ml normal saline in each wound. There was one injection at the first day of the creation of the wound and the15th day respectively.③Specimens were collected in3,7,11,15,18,30,60day after surgery. Histological examination are performed on the HE stained specimens. Then the scar proliferation index and the quantity of fibroblasts of each slices were calculated under light microscopy and analyzed with statistics. Using immunohistochemical method, compare protein expression differences of VEGF, cox-2, Bcl-2and Bax in proliferation pieces. Do correlation analysis in immunohistochemical results.Results①Compared with normal saline group (Group S), Group T showed a statistically significant (P<0.05) reduction on scar proliferation index of rabbit ears hyperplastic scar.②Compared with normal saline group (Group S) on the epithelial time, Group T showed a statistically significant (P<0.05) promotion on scar healing of rabbit ears hyperplastic scar.③The observation under light microscopy of HE staining slice of postoperative15,30,60day indicated that: Early hyperplasia block has a large number of fibroblasts, given priority to collagen in later period; In normal saline group (group S), the scar tissue in the dermis was obviously thickening, fibroblasts and muscle fibroblasts were more than BTXA group (Group T); the dermis contained a large number of dense and thick collagen fiber, which were chaotically arranged in a spiral or nodular shape, forming collagen nodules; In BTXA group (Group T), there were thinner dermis in scar tissue, and less fibroblast cells and muscle cells; the fibroblast collagen fiber decreased in density, arranged regularly and horizontally in surface; the spiral structure decreased.④The calculation of the quantity of positive cells among the protein expression of VEGF and cox-2, Bcl-2and Bax in immunohistochemical slices of postoperative30,60day indicated that:There were statistical significantly (P<0.05) more protein expression of VEGF, cox-2and Bcl-2in normal saline group (Group S) than in BTXA group (Group T).There were statistical significantly (P<0.05) less protein expression of Bax in normal saline group (Group S) than in BTXA group (Group T).⑤The correlation analysis of cox-2and VEGF protein expression showed that there was a positive correlation between them. The correlation analysis of cox-2and the Bcl-2protein expression showed that there was no significant correlation. The correlation analysis of the Bcl-2and Bax protein expression showed that there was negative correlation between them.Conclusion①After fully healed, the rabbit ear ventral full-thickness skin can perform similar hyperplastic scar as human in a certain period of time.②The model of rabbit ear scar is a simple, economical and repeatable animal model. It can be used as an experimental animal model in dynamic research of drugs action on hyperplastic scar.③BTXA can obviously inhibit the formation of rabbit ear hyperplastic scar and can inhibit hyperplasia of scar tissue. It can also inhibit contracture.pf proliferative scar at the same time.④This report provides a further confirmation that the mechanism of BTXA inhibiting rabbit ear scar hyperplasia and contracture may achieve by suppressing the proliferation of (muscle) fiber cell, and inhibiting the express of VEGF and Cox-2to reduce the synthesis of collagen.⑤BTXA inhibiting rabbit ear scar hyperplasia may achieve by reducing the synthesis of collagen from promoting scar cell apoptosis.⑥BTXA inhibiting rabbit ear scar hyperplasia may achieve by promoting cell apoptosis from inhibiting the Bcl-2protein expression and promoting Bax protein expression. |
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