Effects and mechanism of urinary kallidinogenase in the survival of random skin flaps in rats

Abstract Objective This study explored the effects of urinary kallidinogenase (UK) on ischemia and necrosis of random skin flaps in rats, and the mechanisms thereof. Methodology Ischemia and necrosis of random skin flaps were induced by constructing a modified McFarlane flap model on the dorsa of rats. UK (0.016 PNA/kg) or normal saline (10 ml/kg, control) was administered through the tail vein immediately after flap ischemia model construction and then daily for 7 days. After sacrifice, the flap tissue was harvested and stained with hematoxylin and eosin (H&E), and histopathological changes were observed. Lead oxide/gelatin angiography and laser Doppler imaging were performed to demonstrate angiogenesis and changes in blood flow. Immunohistochemical analysis of the H&E-stained slices was performed to detect the expression of vascular endothelial growth factor (VEGF), interleukin (IL)-1β, IL-6, and tumor necrosis factor-α (TNF-α). The TNF-α and IL-6 levels were also detected by enzyme-linked immunosorbent assays. The activity of superoxide dismutase (SOD) and the malondialdehyde (MDA) content were measured to represent the oxidative damage level. Results UK significantly alleviated ischemia and necrosis of random skin flaps, as evidenced by improved general results and histopathological manifestations, and markedly increased the mean survival area. UK prompted angiogenesis, increased blood flow and VEGF expression. The levels of TNF-α, IL-6, and IL-1β were declined. Furthermore, UK increased SOD activity and decreased MDA content, suggesting that it has the capacity to alleviate oxidative damage. Conclusion These findings suggest that UK sufficiently attenuated flap ischemia and increased the survival of random skin flaps in rats.