Flap Survival In Rats Research Articles

Irisin pre-treatment promotes multi-territory perforator flap survival in rats: An experimental study

BackgroundThe present study was designed to investigate the effects of irisin pre-treatment on multi-territory perforator flap survival and blood vessels of Choke II zone in rats and to explore the underlying mechanism. MethodsEighty adult Sprague-Dawley (SD) rats were divided into the Irisin group and the saline group (N = 40 each), and subjected to multi-territory perforator flap operations on the left flank. Rats in the irisin group were intraperitoneally injected with irisin (40 ng/kg), and rats in the control group were intraperitoneally injected with normal saline. Seven days after operation, we calculated the surviving flap area was calculated, and measured the density of microvessels, epidermal growth factor and blood flow in Choke II zone. ResultsIrisin pre-treatment could improve the flap survival area, increase average density of microvessels and up-regulate the mRNA and protein level of vascular endothelial growth factor, thereby promoting flap angiogenesis. ConclusionIrisin improved flap blood supply and increase the survival rate of multi-territory perforator flap by promoting angiogenesis of flank multi-territory perforator flap survival in Choke II zone.

Protective effect of citicoline on random flap survival in a rat mode

BackgroundMedical therapy for flap survival has been extensively investigated. In this study, we explored the effect of citicoline (CDP-choline, CDPC), used for clinical treatment of cerebral trauma, on random skin flap survival in rats. Materials and methodsSixty rats were divided into three groups: low-dose (CDPC-L), high-dose (CDPC-H), and control. The CDPC-L and CDPC-H groups were intraperitoneally injected with 100 mg/kg and 300 mg/kg CDPC every day, respectively; the control group was injected with an equivalent volume of normal saline. The survival region was assessed on the 7th day after the flap operation. The microvascular density and neutrophil density were measured by hematoxylin and eosin staining. Lead angiography was used to detect angiogenesis, and laser Doppler was used to detect blood perfusion. Expression levels of vascular endothelial growth factor (VEGF), interleukin (IL)-1β, IL-6, tumor necrosis factor (TNF)-α, Toll-like receptor (TLR) 4, and nuclear factor kappa B (NF-κB) were detected by immunohistochemistry. Malondialdehyde and superoxide dismutase were used to determine the lipid peroxidation level. ResultsThe average survival region of the flap was significantly larger in the CDPC-H group than in CDPC-L and control groups, with less ischemic necrosis. VEGF expression, microvascular density, angiogenesis, blood perfusion, and superoxide dismutase in the flap were higher in the CDPC-H group than in the CDPC-L and control groups. In addition, levels of neutrophil density, IL-1β, IL-6, TNF-α, TLR4, NF-κB, and malondialdehyde decreased significantly in the CDPC-H group. ConclusionHigh-dose CDPC injection after a random flap operation is beneficial for flap survival.

Hyperoxygenated solution improves tissue viability in an avulsion injury flap model

Management of avulsion injuries remains a challenge due to necrosis. The aim of the present study is to create an experimental model reproducing an avulsion injury and investigate the effects of hyperoxygenated solution (HOS), a method of oxygen delivery that has been widely used in the therapy of ischaemia-hypoxia diseases, on avulsion injury flap survival in rats. Forty male rats were divided into four groups (n = 10 each). Dorsal random pattern flaps measuring 3 × 9 cm, including the panniculus carnosus, were elevated and run over by the skin avulsion model machine, and the flaps were then sutured into their original places. The sham+HOS and avulsion+HOS groups received intravenous HOS (20 ml/kg) each day for 7 days after the operation. The sham+saline and avulsion+saline groups received intravenous saline solution (20 ml/kg) each day for 7 days after the operation. Percutaneous O2 pressure (TcpO2) measurement, serial examinations of skin flap blood perfusion, skin flap survival evaluation and histopathology were performed to assess the efficacy of HOS on avulsion injury. Compared to the avulsion+saline groups, TcpO2 was significantly higher in the avulsion+HOS groups at 15, 30 and 60 min after infusion (P<0.05). The blood perfusion of flaps in the avulsion+HOS group was higher than in the avulsion+saline group (P<0.05). The survival rate was higher in the avulsion+HOS group than in the avulsion+saline group (P<0.05), and the histopathology assays supported the data. We succeeded in developing an avulsion injury model and demonstrated that HOS could improve the survival of the avulsion injury flaps in rats by effectively increasing the local oxygen content and blood perfusion and ameliorating inflammatory damage.

Incretin Mimetics Vildagliptin and Exenatide Improve Pedicle Skin Flap Survival in Rats.

Incretin Mimetics Vildagliptin and Exenatide Improve Pedicle Skin Flap Survival in Rats.

Effects of adiponectin on random pattern skin flap survival in rats

BackgroundRandom flaps are commonly used to repair wounds and improve the clinical appearance. However, flap necrosis is frequently encountered in the clinical setting. Adiponectin is a biologically active endogenous polypeptide secreted by adipocytes that can reduce oxidative stress, inflammation, and apoptosis. This study was performed to explore the effects of adiponectin on the survival of random flaps in rats. Materials and methodsThirty-six healthy rats were divided into two groups, i.e., an adiponectin group and a control group. A modified McFarlane flap was created on the backs of the rats. The area of flap survival was gauged after sacrifice of the rats on day 7 after surgery, and the tissue samples were subjected to histological analysis. Angiogenesis was assessed by oxide-gelatin angiography, laser Doppler imaging, and immunohistochemistry. Pathological changes in the flaps were examined by hematoxylin and eosin staining. The level of oxidative stress was evaluated using malondialdehyde (MDA) and superoxide dismutase (SOD) kits. ResultsThe adiponectin group had a larger tissue survival area and less edema compared with the control group. VEGF expression and SOD activity were markedly increased, but the MDA level was significantly decreased, in the adiponectin group. Histological analysis showed that adiponectin promoted angiogenesis and inhibited inflammation. ConclusionsAdiponectin is useful for improving random skin flap survival.

The Effect of Leonurine on Multiterritory Perforator Flap Survival in Rats

BackgroundLeonurine (Leo), a natural active compound of Leonurus cardiaca, has been shown to possess various biological activities. However, it is not known whether Leo promotes perforator flap survival. MethodsIn this study, a perforator flap was outlined in the rat dorsum. The rats that survived surgery were divided randomly to control and Leo groups (n = 36 per group). Flap viability, flap perfusion, and level of protein linked with oxidative stress, cell apoptosis, and angiogenesis were evaluated. ResultsRelative to control group, the Leo group showed significantly higher the flap survival percentage (70.5% versus 90.2%, P < 0.05) and blood perfusion (197.1 versus 286.3, P < 0.05). Leo also increased 1.8-fold mean vessel density and upregulated 2.1-fold vascular endothelial growth factor protein expression compared with the control group, both of which indicate increased angiogenesis. Moreover, it significantly inhibited apoptosis by lowering caspase-3 activity. Superoxide dismutase expression was remarkably elevated in Leo group compared with the control group (56.0 versus 43.2 U/mg/protein, P < 0.01), but malondialdehyde quantities were significantly lower in the Leo group compared with control group (41.9 versus 57.5 nmol/mg/protein, P < 0.05). ConclusionsLeo may serve as an effective drug for improving perforator flap survival in rats via antioxidant and antiapoptotic mechanisms and promotion of angiogenesis.

Effect of fractional ablative carbon dioxide laser with lidocaine spray on skin flap survival in rats.

BackgroundLidocaine spray is a local anesthetic that improves random-pattern skin flap survival. The fractional ablative carbon dioxide laser (FxCL) produces vertical microchannels that delivers topically applied drugs to the skin. In this study, we hypothesized that FxCL therapy would enhance the lidocaine effect to improve random-pattern skin flap survival in rats.MethodsMcFarlane random-pattern skin flaps were elevated in 48 rats, which were divided into four groups according to treatment: FxCL+lidocaine, FxCL, lidocaine, and nontreatment (control). On postoperative day 7, necrotic flap areas, the number of capillary vessels, and neutrophil count were evaluated. Anti-rat vascular endothelial growth factor (VEGF) and CD31 antibody activity were also evaluated by immunohistochemical staining.ResultsFlap survival rate was 53.41%± 5.43%, 58.16%± 4.80%, 57.08%± 5.91%, and 69.08%±3.20% in the control, lidocaine, FxCL, and FxCL+lidocaine groups, respectively. Mean neutrophil count in the intermediate zone excluding the necrotic tissue was 41.70± 8.40, 35.43± 6.41, 37.23±7.15, and 27.20± 4.24 cells/field in the control, lidocaine, FxCL, and FxCL+lidocaine groups, respectively. Anti-rat VEGF and CD31 antibody activity were the highest in the FxCL+lidocaine group.ConclusionFxCL with lidocaine had a positive effect on random-pattern skin flap survival in rats. Thus, FxCL with lidocaine spray should be considered as a new treatment option to improve flap viability.

The beneficial effects of subcutaneous Allium cepa injection on random flap survival in rats

Random flaps are frequently used in the practice of reconstructive surgery. The aim of this experimental study was to investigate the effects of Allium cepa on random flap survival in rats. Fourteen Wistar rats were used for this experimental study. The subjects were divided into experiment and control groups. Rats in the experiment group received daily injections of A. cepa extract for 7 d before the elevation of the flaps. Following the treatmentperiod, elevation and reinsertion of the dorsal flaps were performed. Necrotic and total flaps areas were marked and calculated 7 d after the flap elevation. Histological examinations and microangiography were performed to evaluate the results. The mean value of the proportion of necrotic flap areas to the total flap area was 25.06 and 50.6% in the A. cepa and control group, respectively (p = .0079). In the histological examination, number of vessels identified in the dermis were 23.75 ± 0.7 and 33.75 ± 9 in the A. cepa and control group, respectively (p = .7457). In angiographic images, vessels formations were more noticeable in the A. cepa group. We conclude that preoperative subcutaneous A. cepa injection increases dorsal flap survival in rats.

Effects of bradykinin on the survival of multiterritory perforator flaps in rats

BackgroundBradykinin, a vasoactive peptide, has many biological functions. For example, it accelerates angiogenesis. Thus, we studied the effects of bradykinin on the survival of perforator flaps.MethodsAveragely, 50 male Sprague–Dawley rats were divided into control and bradykinin groups and underwent procedures to the multiterritory perforator flap. Areas of flap survival were tested 7 days later. Flap perfusion was evaluated by laser Doppler imaging. We assessed the extent of autophagy by determining LC3-II/I, Beclin 1, and p62. Flap angiogenesis was assessed by immunohistochemistry and H&E staining. We measured the level of vascular endothelial growth factor (VEGF) protein using western blot. We assessed oxidative stress by measuring the activity of superoxide dismutase (SOD) and malondialdehyde (MDA) levels. The apoptotic index was also evaluated by western blot, and we determined nitric oxide (NO) production using an NO assay kit.ResultsThe bradykinin group exhibited significantly larger areas of flap survival, higher blood supply, and more neovascularization. The bradykinin group also had higher SOD activity, higher VEGF expression and NO content, and reduced MDA compared to the control group. Rats treated with bradykinin also had lower levels of apoptosis and autophagy relative to the control group.ConclusionOur results suggest that bradykinin promotes the survival of multiterritory perforator flaps by increasing angiogenesis, promoting the release of NO, suppressing apoptosis, reducing oxidative stress, and inhibiting autophagy.

Subdermal nitrous oxide delivery increases skin microcirculation and random flap survival in rats

Random skin flaps are essential tools in reconstructive surgery. In this study, we investigated the effect of subdermal nitrous oxide (N2O) application on random flap survival. In this experimental study, we used 21 female rats in three groups. In the N2O and air groups, gases were administrated under the proposed dorsal flap areas daily for seven days. Following the treatment period, flaps were raised and inserted back into their place from the dorsal skin. In the control group, the flaps were elevated and inserted back to their place without any pretreatment. Calculation of necrotic flap areas, histological examination and microangiography was performed to evaluate the results 7 days after the flap surgery. The average of necrotic flap area in the N2O, air and control group was 13.45%, 37.67% and 46.43%, respectively. (N2O vs air p = .044; N2O vs control p = .003). The average number of capillary formations identified in the histological analysis was 7.0 ± 1.58, 3.75 ± 2.36 and 4.4 ± 0.54 in the N2O, air and control group, respectively. (N2O vs air p = .017; N2O vs control p = .037). The average number of capillary structures identified in the angiography images were 6.3 ± 1.52, 1.6 ± 1.15 and 1.3 ± 0.57 in the N2O, air and control group, respectively. (N2O vs air p = .04; N2O vs control p = .02). We conclude that subdermal N2O application increases random flap survival through an increase in the skin microcirculation and could be promising for future clinical applications.

Oral administration of alanyl-glutamine and glutamine improve random pattern dorsal skin flap survival in rats.

Objective(s):Skin flap necrosis is the most common postoperative side effect in reconstructive surgeries. Glutamine (GLN) has been shown to accelerate wound healing process. The purpose of this study was to evaluate the effects of GLN either in free form or in the dipeptide form along with L- alanyl (Ala-GLN) on random skin flaps survival in rats.Materials and Methods:Dorsal skin flaps with caudal bases (8 ×2 cm) were established in 24 adult male Wistar rats. Then, the animals were randomly assigned into 3 groups (n=8). Control, GLN (0.75 g/kg) and Ala-GLN (0.75 g/kg). All groups administrated orally 24 and 6 hr before flap elevation and continued repeatedly daily until 7 days postoperation. The flap survival rate and vascular density using histological analysis were evaluated. Vascular endothelial growth factor (VEGF) by immunohistochemical method was determined.Results:Seven days after surgery, the mean surviving area in the GLN and Ala-GLN groups were significantly greater than in the untreated control group (P<0.001). Furthermore, in comparison with the control group, the number of blood vessels and VEGF-positive cells in treated groups with GLN and Ala-GLN were significantly higher. However, no significant differences were observed between treated groups with GLN and Ala-GLN.Conclusion:The findings from this study indicate that oral administration of GLN in free form or in the dipeptide (Ala-GLN) could promote neovascularization and improve skin flap survival in rats.

Varenicline increases random flap survival in rats submitted to nicotine

Smoking is a leading cause of flap failure. Varenicline-assisted smoking cessation has shown beneficial effects on vascular endothelial function. The aim of this study was to determine whether varenicline conveys beneficial effects for skin flap survival. Twenty-four rats were randomly divided into four groups of six. The rats in the control group received normal saline subcutaneous injections, and those in the nicotine group received subcutaneous nicotine injections. The rats in the varenicline group received varenicline intraperitoneally, and those in the nicotine-varenicline group received both nicotine and varenicline. At the end of week 3, the dorsal skin flaps were raised in all rats. On postoperative day 7, the flaps were evaluated by direct observation, microangiography, and light microscopy. The mean necrotic area of the flaps was significantly greater in the nicotine group than in the control group (49.2 ± 4.71 vs. 22.03 ± 0.93%, respectively, p < .01) and significantly higher in the nicotine-varenicline group than in the varenicline group (22.4 ± 1.23 vs. 9.2 ± 0.59%, respectively, p < .01). However, no significant difference was observed between the control and nicotine-varenicline groups (p = .934). Microangiographically, vascularity was lowest in the nicotine group and highest in the varenicline group. Histologically, larger areas of necrosis, more severe inflammation and less vessel formation were observed in the nicotine group. Healing, exhibited by a greater number of vessels, was evident in the varenicline-applied groups. Varenicline appears to increase the microcirculation of random flaps, as shown by decreased flap necrosis and increased vascularity.

Effects of curculigoside A on random skin flap survival in rats

Necrosis in distal areas of random skin flaps remains a challenging issue. Curculigoside A (CA), one of the main bioactive phenolic compounds, has been reported to induce angiogenesis in vitro by increasing proliferation, tube formation, and migration. In addition, CA was shown to increase vascular endothelial growth factor (VEGF) expression. In this study, we investigated the potential use of CA as a novel candidate to enhance the viability of the ischemic skin flap. A modified McFarlane flap was used as a surgical model in Sprague-Dawley rats. Three groups of rats were treated as follows: the control group received 0.9% saline orally, while rats in the two treatment groups were administered 10 mg/kg or 20 mg/kg CA orally for 7 days, respectively. On day7, the mice were killed, and tissue samples were collected for hematoxylin and eosin staining and immunohistochemical examination, while laser Doppler imaging and oxide-gelatin angiography were performed to assess angiogenesis. Kits for the analysis of superoxide dismutase (SOD) and malondialdehyde (MDA) were used to verify the oxidative stress level. Treating animals with CA significantly increased the surviving portion of the flaps. VEGF and SOD expression and microvessel development were markedly increased, and the MDA level was reduced, in the CA treatment groups. Histological studies demonstrated that CA promoted angiogenesis and attenuated inflammatory cell numbers. These findings indicated that CA increases random skin flap survival.

Effects of Morroniside on the Viability of Random Skin Flaps in Rats

ABSTRACTObjective: The purpose of our experiment was to determine whether morroniside can improve the survival of ischemic skin flaps in rats. Methodology: A total of 40 male Sprague-Dawley rats were randomly divided into two groups (control group and treatment group). Modified McFarlane flaps were performed (causally based, 9 cm × 3 cm). The percentage of survival of each flap was calculated. Flap blood flows were measured by Laser-Doppler flowmeter. Flap vasculature was assessed by angiography after Lead oxide-gelatin injection. Vascular endothelial growth factor (VEGF) was evaluated by immunochemistry. Superoxide Dismutase (SOD) level and malondiadehyde (MDA) content were determined using assay kits. Results: At the seventh postoperative day, the morroniside-treated rats showed a higher percentage of flap survival than the control rats. Flap perfusion and the level of vascular endothelial growth factor were significantly elevated in the morroniside-treated group. In the treatment group, the distal section of the flap was nearly saturated with contrast agent, while in the control group, the contrast agent perfused only half of the flap. In the treatment group, morroniside administration significantly increased SOD level and reduced MDA content. Conclusion: Morroniside can enhance ischemic flap survival.

Preoperative subcutaneous sildenafil injection increases random flap survival in rats.

To investigate the effect of subcutaneous sildenafil on random flap survival. Fourteen Wistar rats, which were divided in to two groups, were used for this experimental study. Rats in the sildenafil group received subcutaneous sildenafil injections daily for seven days before flap elevation. At the end of the treatment period, 9x3 cm dorsal skin flaps were elevated and reinserted back into their place in all of the animals. Necrotic and whole flaps areas were recorded on graph papers. Seven days after the flap elevation samples for histological examination were taken and angiographies were performed to visualize the flap vascularization. The calculated average percentage of necrotic flap areas were 18.29% and 42.26% in the sildenafil and control group respectively.(p=0.0233). In selected angiography images, vessels were found to be more prominent in the sildenafil group. The average number of capillary formations under light microscopy was higher in the sildenafil group (p= 0.0286). The subdermal high dose sildenafil has a positive effect on flap survival.

Human and Autologous Adipose-derived Stromal Cells Increase Flap Survival in Rats Independently of Host Immune Response.

There is a rising interest in adipose-derived stromal cells for clinical use; however, it is unknown whether freshly isolated stromal cells (SVF) or culture-expanded cells (ASCs) are more efficacious. We therefore aimed to compare the 2 cellular therapies in an in vivo model of angiogenesis, the ischemic flap in rats, which induces acute ischemia. We also aimed to determine the importance of cell presence and the host immune response. A total of 96 rats (n = 12 in each group) were used, and in each rat, a caudally based random flap measuring 2 × 7 cm was made. The study was conducted in 3 phases. First, each rat was treated with human SVF cells, human ASCs, or vehicle. Second, each rat was treated with human SVF, human SVF lysate, or vehicle. Finally, each rat was treated with rat (autologous) SVF cells or vehicle. Flap survival, vessel density, and stromal cell retention were evaluated after 7 days. The mean survival rates for SVF treatment regardless of human or autologous origin were significantly increased as compared with the control group. Adipose stem/stromal cell and SVF lysate injection did not increase flap survival. Vessel density was increased for human and rat SVF and human ASC but not for SVF lysate. Human cells were not detected in the flaps after 7 days. Flap survival increased with SVF treatment regardless of human or autologous origin, suggesting that increased flap survival is independent of the host immune response. All cell injections lead to increased vessel density, but it did not necessarily lead to increased flap survival. Further research should elaborate which molecular events make SVF treatment more efficacious than ASC.

Naringin improves random skin flap survival in rats.

BackgroundRandom-pattern flap transfer is commonly used to treat soft-tissue defects. However, flap necrosis remains a serious problem. Naringin accelerates angiogenesis by activating the expression of vascular endothelial growth factor (VEGF). In the present study, we investigated whether naringin improves the survival of random skin flaps.ResultsCompared with controls, the naringin-treated groups exhibited significantly larger mean areas of flap survival, significantly increased SOD activity and VEGF expression, and significantly reduced MDA level. Hematoxylin and eosin (HE) staining revealed that naringin promoted angiogenesis and inhibited inflammation.Materials and Methods“McFarlane flap” models were established in 90 male Sprague-Dawley (SD) rats divided into three groups: a 40 mg/kg control group (0.5 % sodium carboxymethylcellulose), a 40 mg/kg naringin-treated group, and an 80 mg/kg naringin-treated group. The extent of necrosis was measured 7 days later, and tissue samples were subjected to histological analysis. Angiogenesis was evaluated via lead oxide–gelatin angiography, immunohistochemistry, and laser Doppler imaging. Inflammation was evaluated by measurement of serum TNF-α (tumor necrosis factor-α) and IL-6 (interleukin-6) levels. Oxidative stress was assessed by measuring superoxide dismutase (SOD) activity and the malondialdehyde (MDA) level.ConclusionNaringin improved random skin flap survival.

Detrimental effect of Hypoxia-inducible factor-1\u03b1-induced autophagy on multiterritory perforator flap survival in rats

Hypoxia-inducible factor-1α (HIF-1α) plays a key role in angiogenesis, improves flap survival, and activates autophagy. The effect of HIF-1α-induced autophagy is still debatable. Thus, we investigated the effect of HIF-1α-induced autophagy on multiterritory perforator flap survival. In this study, 99 male Sprague-Dawley rats received multiterritory perforator flap procedure and were divided into three groups with 33 each. The dimethyloxalylglycine (DMOG) plus 3-methyladenine (3-MA) group received intraperitoneal injection of DMOG (40 mg/kg) and 3-MA (10 mg/kg). The DMOG group and control group received comparative DMOG and saline respectively. On postoperative day (POD) 7, HIF-1α’s activities of flap survival and perfusion improvement were confirmed in DMOG group, however, its positive effects were further enhanced by co-administration of autophagy inhibitor, 3-MA. On POD 1, vascular endothelial growth factor, mean microvascular density and blood perfusion were not affected by HIF-1α up-regulation or autophagy inactivation. However, HIF-1α-induced autophagy augments apoptosis and oxidative stress. The increased level of apoptosis and oxidative stress was reversed by 3-MA and resulted in further flap survival improvement. In conclusion, HIF-1α-induced autophagy has a detrimental effect on multiterritory perforator flap survival and the flap survival was determined by the combined effects of ischemia and reperfusion injury.

Effects of gamma-low dose irradiation on skin flap survival in rats

PurposeSkin flap necrosis due to inadequate blood supply has remained a common postoperative problem in constructive surgery. As low-dose irradiation (LDI) has been shown to promote the wound-healing process, this study aims to investigate whether LDI could increase neovascularization and skin flap survival in rats. MethodsMcFarlane flaps were created in 21 male rats, which were divided into one control and two treatment groups (Ta and Tb). The treatment groups received a whole body single dose of 100cGy gamma ray irradiation before (Tb) and after (Ta) flap surgery. The flap survival area was evaluated after seven days. The skin samples were collected for histological analysis and determining the vascular endothelial growth factor (VEGF) using the immunohistochemical method. Serum malondialdehyde (MDA) was examined with the kit. ResultsThe mean areas of flap survival were 56.7±3.24, 61.7±2.6, and 66.5±3.82 in the control, Tb, and Ta groups, respectively. There were significant differences between the Tb and Ta groups in comparison with the control group (P<0.05 and P<0.01, respectively). Compared with the control group (8.0±0.73), the mean numbers of the blood vessels in the Ta group (22±1.24) and the Tb group (14±1.29) were significantly higher (P<0.001 and P<0.01). Moreover, the mean numbers of the VEGF-positive cells in the Ta group (4.5±1.04) were significantly higher (P<0.05) than the control group (2.5±0.83). However, no significant differences in the MDA levels were observed among the groups. ConclusionThe findings of this study suggest that LDI has the potential to promote neovascularization to improve flap survival.

Effects of Shen-Fu injection on random skin flap survival in rats

ObjectiveThe aim of this study was to determine the effects of Shen-Fu injection treatment on skin flap survival in an experimental random pattern skin flap model in rats. Materials and methodsNinety male Sprague–Dawley (SD) rats were randomly assigned to the SFI-treated groups and normal saline-treated (control) group. SFI (10 or 20ml/kg) or normal saline (10ml/kg) were administered intraperitoneally once daily. On postoperative day 2, malondialdehyde (MDA), superoxide dismutase (SOD), tumor necrosis factor α (TNF-α) and IL-6 were evaluated. Besides, flap survival rate, tissue edema, mean vessel densities, number of neutrophil, flap angiography and vascular endothelial growth factor (VEGF) expression were examined on day 7. ResultsCompared with the control group, the mean survival area in SFI groups were significantly larger showing a possible dose-dependent effect of SFI. SOD activity was increased significantly, as well as the VEGF expression. MDA level, in the test group, however, was decreased. The hematoxylin and eosin (H&E) stained slices revealed that SFI had the angiogenesis promotion effect, meantime inflammation was clearly inhibited in the SFI groups. ConclusionThis study showed that intraperitoneally administered SFI significantly improved random skin flap survival in rats.