Reparative and Inflammatory Changes in Wounds in Animals with Different Resistance to Hypoxia

Abstract

Individual  resistance  to  hypoxia  largely  determines  the  severity  of  inflammatory  processes and, probably, can affect the regeneration of the skin wound.The aim was to study reparative and inflammatory changes in the wound in Wistar rats with different resistance to hypoxia.Material and methods. The study was performed on mature male Wistar rats weighing 300–350 g. Before the experiment, the resistance of animals to hypoxia was determined. Rats were classified as highly resistant to hypoxia (HR), in which the time to take a lateral position in the pressure chamber “at a height” of 11,500 m was more than 360 s (n=5), to low-resistant (LR) – less than 40 s (n=5). A full-thickness wound with a diameter of 16 mm was applied to the animals  in  the  interscapular zone of the back.  On  the  7th  day  after  the infliction of the wound, a histological and  morphometric study was performed. The proliferative activity of cells in the granulation tissue of the wound was determined  immunohistochemically using  the  Ki-67  marker.  Real-time  PCR  was used  to  evaluate  the  level  of expression of the Hif-1α, Nf-κB, and Vegf genes.Results. It was shown that in rats with high resistance to hypoxia, the total number of cells and, among them, the number of inflammatory cells was higher than in rats with low resistance to hypoxia. However, the percentage of inflammatory cells in the compared groups did not differ significantly. Cell proliferative activity, as measured by the number of Ki-67 positive cells, was higher in rats with high resistance to hypoxia. In the granulation tissue of highly resistant to hypoxia rats, the expression of the Vegf gene was statistically significantly higher than in low-resistant animals, while there were no statistically significant differences in the level of expression of the Hif-1α, Nf-κB genes.Conclusion. In rats with high resistance to hypoxia, on the 7th day of healing of a full-thickness skin wound, reparative processes in it are more pronounced. In  the  horizontal  layer  of  fibroblasts,  there  are  more  cells,  among  them  inflammatory  ones  -  histiocytes  and macrophages, which is combined with a higher number of proliferating Ki-67 positive cells and the expression level of vascular endothelial growth factor (Vegf).