Abstract
Random skin flaps are often used in plastic surgery, but the complications of marginal flap ischemia and necrosis often limit their wider clinical application. Apigenin (Api) is a flavonoid found in various fruits and vegetables. Api has been shown to promote angiogenesis, as well as reduce oxidative stress, membrane damage, and inflammation. In this study, we assessed the effects of Api treatment on random skin flap survival. Dorsal McFarlane skin flaps were transplanted into rats, which were randomly divided into three groups: control (normal saline), low-dose Api (20 mg/kg), and high-dose Api (50 mg/kg). Seven days after the surgery, the activity of superoxide dismutase (SOD) and the level of malondialdehyde (MDA) were measured. Histological analyses were performed to determine flap survival and tissue edema. H&E staining was performed to assess the histopathological changes in skin flaps, and the levels of microvascular density (MVD) were determined. Laser doppler flowmetry was used to assess microcirculation blood flow. Flap angiography was performed by injection of lead oxide/gelatin. The expression levels of vascular endothelial growth factor (VEGF), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interlukin-1β (IL-lβ) were evaluated by immunohistochemistry. Rats in the high-dose Api group exhibited higher average flap survival area, microcirculatory flow, increased SOD activity, and higher VEGF expression levels compared with the other two groups. Furthermore, the levels of MDA and pro-inflammatory cytokines were significantly decreased in rats treated with high-dose Api. Our findings suggest the potential usefulness of Api in preventing skin flap tissue necrosis.
Highlights
In contrast to axial pattern flaps, random skin flaps lack axial vascularization, due to anatomical differences in blood supply
Macroscopic examination revealed that the extent of necrosis was greater in the control group compared to that in Api-treated rats (Figure 2A)
A previous study showed that Api (20 mg/kg/day) administration significantly attenuated early brain injury, which includes brain edema, blood–brain barrier disruption, neurological deficiency, and cell apoptosis, after subarachnoid hemorrhage in rats by suppressing the expression of toll-like receptor 4 (TLR4), nuclear factor-κB (NF-κB), and their downstream pro-inflammatory cytokines in the cortex and by upregulating the expression of tight junction proteins of the blood–brain barrier (Zhang et al, 2015)
Summary
In contrast to axial pattern flaps, random skin flaps lack axial vascularization, due to anatomical differences in blood supply. The length-to-width ratio of the flap should not exceed 2:1 because the lack of flap vascularization increases the risk of distal ischemia and necrosis. In the face and neck, the Apigenin on Random Skin Flap length-to-width ratio can be increased to 2.5:1, due to the good vascularization of these tissues. The production of reactive oxygen species (ROS) and other inflammatory mediators by these immune cells aggravate ischemia and tissue damage (Kang et al, 2014). The development of strategies to promote angiogenesis and improve local blood supply, as well as inhibit the production of inflammatory mediators and ROS, is crucial for improving the survival of random skin flaps
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