Wound healing mechanisms in rats with streptozotocin-induced diabetes mellitus

Background. Wound healing disorders and formation of diabetic foot, a severe disabling complication of diabetes mellitus, are accompanied by nervous system impairment and/or ischemia. Objective — the study was aimed at assessing the effect of peripheral innervation disorders on the regulation of tissue repair in the streptozotocin-induced rat model of diabetes mellitus. Material and methods. The study was carried out in male white outbred rats (n=70). The animals were wounded 42 days after induction of diabetes by injecting streptozotocin (diabetes group; this group received insulin Levemir at a dose of 2 units/kg in saline subcutaneously to reduce mortality), or after injection of citrate buffer (CB group). Skin samples were taken on day 8, 16, and 24 after wound modeling. Pain sensitivity was assessed in all animals. The resulting skin fragments were fixed, dehydrated, and embedded in paraffin according to standard procedures. Sections were stained with hematoxylin and eosin, antibodies specific for Ki-67, α 1 , β 1 , and β 2 -adrenoreceptors were used for immunohistochemical staining. Intact animals were used as an additional control group. Results. Tail withdrawal time measured on day 56 was higher in DM group rats as compared to the control group (p=0.017). CB group demonstrated a tendency towards more rapid wounds healing than diabetic animals, although the difference was not statistically significant due to wide scatter of data in the DM group (p=0.64). The intensity of staining for Ki67 was lower in the DM group (p=0.045). Reduced density of β 2 -adrenoreceptors was observed at the areas remote from the wound in CB group rats. Conclusion The results show no correlation between altered innervation and impaired tissue repair in rats with streptozotocin-induced diabetes.