A recombinant plasmid encoding human hepatocyte growth factor promotes healing of combined radiation-trauma skin injury involved in regulating Nrf2 pathway in mice.

Combined radiation-trauma skin injury represents a severe and intractable condition that urgently requires effective therapeutic interventions. In this context, hepatocyte growth factor (HGF), a multifunctional growth factor with regulating cell survival, angiogenesis, anti-inflammation and antioxidation, may be valuable for the treatment of combined radiation-trauma injury. This study investigated the protective effects of a recombinant plasmid encoding human HGF (pHGF) on irradiated human immortalized keratinocytes (HaCaT) cells in vitro, and its capability to promote the healing of combined radiation-trauma injuries in mice. The pHGF radioprotection on irradiated HaCaT cells in vitro was assessed by cell viability, the expression of Nrf2, Bcl-2 and Bax, as well as the secretion of inflammatory cytokines. In vivo therapeutic treatment, the irradiated mice with full-thickness skin wounds received pHGF local injection. The injuries were appraised based on relative wound area, pathology, immunohistochemical detection, terminal deoxynucleotidyl transferase dUTP nick end labelling assay and cytokine content. The transfection of pHGF increased the cell viability and Nrf2 expression in irradiated HaCaT cells. pHGF also significantly upregulated Bcl-2 expression, decreased the Bax/Bcl-2 ratio and inhibited the expression of interleukin-1ß and tumor necrosis factor-α in irradiated cells. Local pHGF injection in vivo caused high HGF protein expression and noticeable accelerated healing of combined radiation-trauma injury. Moreover, pHGF administration upregulated Nrf2, vascular endothelial growth factor, Bcl-2 expression, downregulated Bax expression and mitigated inflammatory response. In conclusion, the protective effect of pHGF may be related to inhibiting apoptosis and inflammation involving by upregulating Nrf2. Local pHGF injection distinctly promoted the healing of combined radiation-trauma injury and demonstrates potential as a gene therapy intervention for combined radiation-trauma injury in clinic.

Research progresses in the mechanism and treatment of the impaired wound healing of combined radiation?trauma injury / 中华放射医学与防护杂志

Combined radiation-trauma injury is mainly observed in radiation treatment of cancer and radiation injury with traumatic patients. The prominent problem of combined radiation-trauma injury is delayed or prolonged wound healing. The mechanism of the impaired wound healing is complicated, and the current effective treatment method are limited. This paper reviews the mechanism and treatment of this impaired wound healing, including the cellular depletion, stromal cell dysfunction, aberrant collagen deposition, microvascular damage, as well as the targeted therapies for the impaired wound healing such as stem cell repletion, antioxidant therapy, transforming growth factor beta-1 ( TGF-β1 ) modulation, and implantable biomaterials. This paper is designed to provide a reference for further deep research on the mechanism and treatment of radiation-trauma injury.

Evaluation of wound healing of skin defect in mice with radiation injury / 第二军医大学学报

Objective To establish mouse models of total body irradiation (TBI) with different doses of 60 Co 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 60 Co ray. Within 30 min after irradiation,a full thickness square wounds (1.5cm×1.5cm) 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, fibro blasts 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,and8 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 (P<0.01), and that in 4 Gy group was significantly larger than that in the control group on the 8th day (P<0.05). 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 60 Co 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.