Effect of paeoniflorin on distal survival of random flaps

Background: Distal ischemic necrosis is a common complication of orthopedic random skin flaps surgery. Paeoniflorin, a natural compound extracted from Paeonia lactiflora, can enhances angiogenesis and alleviates excessive inflammatory response. We investigated the changes of ischemic extra-long flaps with paeoniflorin and its possible mechanism.Methods: We raised dorsal McFarlane flaps in 54 Sprague-Dawley rats. We designed three groups of rats: highpaeoniflorin group (HP, 50 mg/kg/d), low-paeoniflorin group (LP, 20 mg/kg/d), and control group. The flap survival rate was calculated, seven days after flap construction. Blood perfusion was detected by laser Doppler flow imaging, and angiogenesis was detected by Lead oxide/gelatin angiography. Oxidative stress levels of flaps were determined by detecting superoxide dismutase (SOD) and malondialdehyde (MDA). The histopathological status of flap was evaluated by hematoxylin and eosin (H&E) staining. Immunohistochemistry was used to determine the expression of high mobility group protein B1 (HMGB1), nuclear factor-kappa B (NF-icB), Toll-like receptor 4 (TLR4), tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-6, IL-113, IL-18, vascular endothelial growth factor (VEGF), cysteine protease-1 (caspase-1) and NLPR3.Results: The flap survival rates and SOD activity in the experimental groups were significantly higher, while MDA activity was lower. Experimental groups showed significantly improved microcirculatory blood flow to the flap and increased angiogenesis. Immunohistochemistry revealed that paeoniflorin was associated with significantly increased VEGF expression, and decreased level of HMGB1, TLR4, TNF-alpha, NF-icB, IL-6, IL-113, caspase-1, NLPR3, and IL-18.Conclusions: Paeoniflorin effectively enhanced the survival of rat random skin flaps by promoting vascular hyperplasia, inhibiting pyroptosis, and down-regulating inflammation.