Effects of Atorvastatin Calcium on the Survival of Ultra-long Dorsal Random Skin Flaps in Rats

  Objective  To investigate the effects of atorvastatin calcium (ATR) on the survival of ultra-long dorsal random skin flaps in rats.

  Methods  Thirty SD rats were divided into five groups (n=6) according to the random number table: normal saline control group (CON group), ATR 10 mg/kg group (P10 group), ATR 20 mg/kg group (P20 group), ATR 30 mg/kg group (P30 group), and ATR 40 mg/kg group (P40 group). After pretreatment with ATR or 0.9% saline for 3 days, an ultra-long dorsal random skin flaps with size of 8 cm×2 cm was made on the back of each rat and replanted in situ. After the operation, the ATR or saline treatment lasted for 3 d. Seven days after operation, the appearance of skin flaps was observed with naked eyes, the survival rate of skin flaps was calculated. The pathological changes in the surviving areas of skin flaps were observed by HE staining, the number of microvessels in skin flaps was observed by immunohistochemistry staining, the mRNA expressions of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) were tested by quantitative real-time PCR, and the contents of superoxide dismutase, nitrogen monoxide and malonaldehyde were tested by enzyme linked immunosorbent assays (ELISA).

  Results  On the 7^th day after operation, the skin flap of the CON group showed a large area of necrosis, and the necrotic part formed crusts. Crusts were hard and inelastic, and a large amount of tissue fluid exudated. The fascial layer showed dark purple. No exudation of tissue fluid was observed in the flaps of P10, P20, P30 and P40 groups. The scab shell fell off naturally and the fur grew normally. HE staining of CON group showed that a large number of inflammatory cell infiltration, epidermal loss and necrosis in skin flaps, but the pathological changes in skin flaps were significantly improved after treatment with ATR. Compared with the CON group, the survival rate of skin flaps, the number of microvessels in skin flaps and the levels of VEGF mRNA, bFGF mRNA, SOD, NO in skin flaps also increased with the dose of ATR, which reached a peak at 30 mg/kg ATR (P<0.05). However, the level of MDA in skin flaps decreased with the dose of ATR, which reached the lowest at 30 mg/kg ATR (P<0.05).

  Conclusion  ATR can enhance the survival of ultra-long dorsal random skin flaps in rats, which may be related to promoting microangiogenesis and inhibiting inflammatory and oxidative stress.