Evaluation of wound healing of skin defect in mice with radiation injury

Objective To establish mouse models of total body irradiation(TBI) with different doses of 60Co γ radiation combined with skin defect,so as to investigate the influence of TBI on wound healing and the pathophysiological changes in combined radiation injury and skin defect.Methods A total of 180 female Kunming mice were irradiated with a single dose of 4,6 or 8 Gy 60Co γ ray.Within 30 min after irradiation,a full thickness square wounds(1.5 cm×1.5 cm) was made on the back of mice to establish animal models of TBI combined with skin defect(n=50),another 30 mice with pure skin defect were used as controls(n=30).Mice in each group were sacrificed on the 3rd,5th,7th,10th and 14th day after injury,each time 6 mice,and the full thickness wounds were harvested.Histological method was used to evaluate the changes of inflammatory cells,fibroblasts and new blood capillaries in the wounds.Image analysis system was used to analyze the areas of the residual wounds.The survival rates and body weight changes of mice within 14 days were analyzed in all groups.Results On the 7th and 14th day after injury,the survival rates of mice in the 6 Gy group were 75% and 55%,respectively.While in the 8 Gy group the survival rate of mice was only 33% on the 7th day,and all the animals died by the 10th day.Within 14 days after injury,the body weight loss of mice demonstrated an increasing tendency with the increase of radiation doses(4,6,and 8 Gy groups).TBI delayed wound healing in mice with the increase of irradiation dose.The unhealed areas in the 6 and 8 Gy groups were larger than that in the control group on the 2nd day(P0.01),and that in 4 Gy group was significantly larger than that in the control group on the 8th day(P0.05).H-E staining showed that the early inflammatory responses were inhibited,the increase of fibroblasts and new capillaries were greatly delayed,and the granulation tissue formation and reepithelialization were slowed down in the TBI group compared with the simple wound group.Conclusion Animal models of TBI with 6 Gy 60Co γ-ray combined with skin defect can serve as a platform to study the mechanism of difficult healing and early treatment of radiation injury combined with skin defect.