Recombinant human growth hormone treatment of mice suppresses inflammation and apoptosis caused by skin flap ischemia-reperfusion injury

Background This study was to investigate the effects of recombinant human growth hormone (rhGh) on ischemia-reperfusion (I/R) injury of mouse flaps. Methods Healthy mice were randomly divided into four groups as follows: sham group, the IR group, the sham+rhGH group and the IR+rhGH group, with 12 mice in each group. Skin pathology was tested by hematoxylin and eosin staining. The flap survival of each group was measured after 7 days. The levels of superoxide dismutase (SOD) and malondialdehyde (MDA) were determined using corresponding kit. The levels of interleukin (IL)-6 and tumor necrosis factor (TNF)-alpha in serum and flap were respectively measured by performing enzyme-linked immunosorbent assay and quantitative real-time (qRT)-PCR. The expressions of cleaved caspase-3, B cell lymphoma/leukemia-2 (Bcl-2), Bcl-2-associated X protein (Bax), vascular endothelial growth factor (VEGF), MnSOD, toll-like receptor 4 (TLR4), and galectin-3 and (p)-p65 were analyzed by RT-PCR or/and Western blot. Results Prophylactic systemic application of recombinant human GH reduced the pathological damage of skin IR and significantly improved the flap survival of IR in mice, accompanied by elevation of VEGF. After administration of recombinant human GH, the activity of SOD/MnSOD in the flap was significantly increased, while the content of MDA was decreased. Cleaved caspase-3 and Bax were downregulated and Bcl-2 was upregulated in IR+rhGH group, compared to IR group. The levels of TLR4, Galectin-3 and p-p65 were decreased by rhGH. Conclusion rhGH had protective effects on flap IR injury, and can be used as a drug intervention target for the treatment of skin flap IR injury.