[Effects and mechanism of retinoic acid on radiation-induced skin injury in mice].

To investigate the effects and mechanism of retinoic acid on radiation-induced skin injury (RSI) in mice. This study was an experimental research. HaCaT cells were obtained and divided into control group (routinely cultured), injury group, treatment group, and antagonism group. The cells in the latter three groups were all exposed to 10 Gy X-ray radiation. The cells in the latter two groups were pretreated with retinoic acid for 12 h before radiation, and the cells in the last group were pre-treated with polyinosinic-polycytidylic acid for 1 h before radiation. Cells from the three irradiated groups at 24 h after radiation and cells from control group at the corresponding time point were collected to detect the reactive oxygen species (ROS) level in the cells by flow cytometry, and measure the protein expressions of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), Toll-like receptor 3 (TLR3), and nuclear factor-κB (NF-κB) in the cells by Western blotting, with the sample number being 3. Twenty-four 6-week-old female BALB/c mice were obtained and divided into control group, injury group, treatment group, and antagonism group according to the random number table method (with 6 mice in each group). The right lower limbs of mice in the latter three groups were all exposed to 35 Gy electron beam radiation to induce RSI. Mice in the latter two groups were treated with retinoic acid at 0 (immediately), 7, 14, 21, 28, 35, and 42 days after injury, while mice in the last group were pre-treated with polyinosinic-polycytidylic acid at these time points. Mice in control group were simulated with sham injury. At 42 days after injury, the wound healing rate was calculated, and blood perfusion (denoted as blood flow index) in the skin tissue at the injury site (i.e. wound tissue) was detected by laser speckle flowmetry; wound tissue was collected, the hematoxylin-eosin staining was performed to count inflammatory cells and measure epidermal thickness, the immunohistochemical staining was performed to detect the expression of IL-6 and TNF-α, the immunofluorescence staining was performed to detect the expression of TLR3, and Western blotting was performed to detect the protein expressions of TLR3 and NF-κB. At 24 h after radiation, the ROS level and protein expressions of IL-6, TNF-α, TLR3, and NF-κB of cells in injury group were significantly higher than those in control group at the corresponding time point (<0.05). The ROS level and protein expressions of IL-6, TLR3, and NF-κB of cells in treatment group were significantly lower than those in both injury group and antagonism group at 24 hours after radiation (<0.05). At 42 days after injury, the wound healing rates of mice in control group, injury group, treatment group, and antagonism group were (100.4±2.7)%, (77.5±2.5)%, (89.8±3.2)%, and (70.1±4.8)%, respectively. The wound healing rate of mice in treatment group was significantly higher than that in injury group and antagonism group (both values <0.05). At 42 days after injury, the blood flow index in the wound tissue of mice in treatment group was significantly lower than that in injury group and antagonism group (both values <0.05). At 42 days after injury, compared with those in control group, the number of inflammatory cells in the wound tissue of mice in injury group was significantly increased, and the epidermal thickness significantly thickened (<0.05); compared with those in treatment group, the number of inflammatory cells in the wound tissue of mice in injury group and antagonism group was significantly increased, and the epidermal thickness significantly thickened (<0.05). At 42 days after injury, the expression levels of IL-6, TNF-α, and TLR3, as well as the protein expressions of TLR3 and NF-κB in the wound tissue of mice in injury group were significantly higher than those in control group (<0.05), while the expression levels of IL-6, TNF-α, and TLR3, as well as the protein expressions of TLR3 and NF-κB in the wound tissue of mice in treatment group were significantly lower than those in injury group and antagonism group (<0.05). Retinoic acid significantly reduces radiation-induced cell injury and promotes the repair of RSI in mice by inhibiting the TLR3/NF-κB signaling pathway and the expression of downstream inflammatory factors.