| Background:The injury of radiation with trauma is called“combined radiation-trauma injure”.The “combined radiation-trauma injure”can be caused by nuclear burst in the war,and usually be found in nuclear accidents, nuclear terrorisms and clinical Radiotherapy,which is characterized by prolonged unhealed wounds. Previous studies suggested that the mechanism is reduction of the number of cells and dysfunction, with the inhibition of growth factors that can be produced by matrix cells.To promote the wound healing in combined radiation-trauma injure has been the focus of study. Platelet-derived growth factor(PDGF) is a kind of polypeptide which can be produced by a variety of cells,It can stimulate the proliferation of mesenchymal cells with a wide range of physiological activity, and plays a significant role in various stages of trauma Repair. Regrenex(0.01% rh-PDGF-BB) had been listed in the United States for the treatment of diabetic foot ulcers, each priced at more than 400 dollars, the high price limited its clinical application. To meet the needs in the military war injury the Institute of Microbiology and Epidemiology of the PLA Academy of Military Medical Sciences based their research on the previous studies, purified from Pichia yeast expression and developed a new recombinant human platelet-derived growth factor(rhThr6- PDGF-BB), with the support of National Science and Technology Major Project(project number: 2011ZXJ09104-03B), our task in this project is to evaluate the pharmacodynamic of the new recombinant human platelet-derived growth factor. A rat model of combined radiation-trauma injure was established to observe the effects of the new ecombinant human platelet-derived growth factor on the wound healing of combined radiation-trauma injure. Our studies aim to provide a theoretical basis for the producing of independent intellectual property wound medicine.Methods:120 Male Wistar rats, 60Co-γ-ray whole body irradiation, the dose of irradiation is 4Gy,followed by a round full-thickness skin wound at a diameter 2cm on the back. Rats Were randomly divided into 6 groups,that is,blank control group, matrix control group, low dose group, middle dose group, high dose group and positive control group with 20 rats in each group. Rats were fed in clean rooms, after daily administration, the conditions of wound healing was observed and documented. Percentage of wound healing area and residual area were both calculated. The morphology of the surface of wound was evaluated by epithelial cell migration, granulation tissue growth and neovascular densities, immunohistochemical assay was used to detect the expression of Bcl-2, PDGF-A and VEGF protein expression.Results: Within 14 d after injury, the median- and high- dose group both healed significantly faster, with the wound almost totally healed in 14 d. while the blank control group healed slower, the wound had not completely healed after 14 d.There was a significant difference(P <0.05) between median- high- dose group and blank control group. The surface of wound in 3 rhThr6-PDGF-BB drug groups exhibited an earlier formation of granulation tissue compared with blank control group and matrix control group. both fibroblasts and new capillaries in drug groups were also more abundant than those in blank control group and matrix control group. Immunohistochemistry revealed a statistically significant increase of Bcl-2,PDGF-A and VEGF in granulation tissues in drug groups compared with controls. There might be some potential mechanism that rhThr6-PDGF-BB accelerate wound healing. On one hand,rhThr6-PDGF-BB can promote local repairing cells chemotaxis and migration to the wound,accelerating cells proliferate;on the other hand,rhThr6-PDGF-BB also stimulate local remnants and inflammatory cells and newborn repairing cells which could express VEGF and PDGF-A. Moreover, rhThr6-PDGF-BB has a function to inhibit apoptosis of cells,it also increase the number of local repairing cells to promote the wound healing.Conclusion: RhThr6-PDGF-BB can remarkably accelerate the wound healing of combined radiation-trauma injury. This result provide a theoretical basis for the advanced research of rhThr6-PDGF-BB. |
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