Objective To research the effects of vascular endothelial growth factor (VEGF) on the survival of reverse flow axial skin flaps. Methods A 8 cm×2 cm full thickness transverse dorsal flap based on right deep circumflex iliacartery was elevated in 20 SpragueDawley rats, which length crossing midline was 4.0 cm. The rats were randomized into two groups:experimental group (n=10), subcutaneous VEGF injections into the flap (200 ng, 200 μl) after flap elevation; controlgroup (n=10), subcutaneous saline injections into the flap (200 μl) after flap elevation. The flap was immediately sutured to its recipient beds then the injection was executed. Seven days after operation, the survival area of flaps and density of vessels were observed and measured, meanwhile its histological representation of the flaps was examined. Results After 7 days of recovery, the mean survival area of flaps was 15.55±0.27 cm2 in experimental group and 13.42±0.57 cm2 in control group. The difference was significant between experimental group and control group (P＜0.01). The mean vessel density of flaps was 21.00±3.16 in control group and 34.40±3.75 in experimental group. The difference was significant between experimental group and control group (P＜0.01). Histological analysis demonstrated that a qualitatively greater amount of granulation tissue, regular collagen fiber and a lot of fibrillated cells were observed in experimental group. Erythrocytes were leaked outfrom vessels, and inflammatory cells were observed around in control group. Conclusion In early survival of flaps, the VEGF can improve the survival of areverse flow axial skin flap through improving angiogenesis and increasing the perfusion of vessel. It is an effective method of improving the survival of reverse flow axial skin flaps that VEGF is fully injected in subcutaneous flaps by single, when flaps are elevated.
ObjectiveTo investigate the effect of simvastatin and mechanical pretreatment on intimal hyperplasia of venous graft and its mechanism.MethodsTwelve New Zealand rabbits were selected and randomly divided into 4 groups: a blank control group, a simvastatin topical treatment group, a mechanical precondition group and a combined group (n=3 in each group). Ultrasound was used to evaluate the changes of graft wall and blood flow velocity in the graft, and pathological section was used to evaluate the intimal hyperplasia. Human umbilical cord endodermal cells were cultured in vitro. A simvastatin group and a solvent control group were set to detect YAP phosphorylation, downstream target gene expression and cell proliferation.ResultsVascular ultrasound showed that except the simvastatin topical treatment group, the flow velocity in vein grafts in the other three groups significantly increased 21 days after surgery compared with 7 days after surgery (P<0.01). Pathological sections showed that the thickness of new intima in the simvastatin topical treatment group, mechanical precondition group, combined group and blank control group were 45.56±4.11 μm, 201.28±16.71 μm, 143.57±7.82 μm, 249.45±13.33 μm, respectively, and there were statistical differences compared with the blank control group (P<0.05). In vitro results showed that compared with the solvent control group, cell death was observed in high concentration simvastatin (5 mmol/L) group, cell proliferation was inhibited in low concentration simvastatin (2.5 mmol/L) group (P<0.05), the expression of YAP protein in the simvastatin group was unchanged, but the expression of phosphorylated YAP protein significantly increased (P<0.05), and the expression of downstream target gene ccn1 was down-regulated (P<0.001).ConclusionIntravascular local application of simvastatin and mechanical preconditioning alone or in combination can inhibit intimal hyperplasia of venous graft. High concentration of simvastatin has cytotoxicity, while low concentration of simvastatin has inhibitory effect on cell proliferation. Simvastatin can inhibit the formation of new intima by inhibiting the entry of YAP into the nucleus and reducing the transcription of cell proliferation-related target gene ccn1.