Experimental Study Of The Effects Of Simvastatin On The Survival Of Random Skin Flaps In Rats

Objective：Statins are 3-hydroxy-3-methylglutaryl coenzyme Areductase inhibitors, as a traditional cholesterol-lowering drug, its pleiotropiceffects have become increasingly important, especially in vascular protection,such as inhibition of smooth muscle cell proliferation and neointimalhyperplasia, promote angiogenesis, improve endothelial function directly,anti-platelet aggregation and inflammatory reaction. Until now，there is fewreport about statins applied in skin flap at a national level．In our study，we tryto investigate the effects of simvastatin on the survival of random pattern skinflaps in rats by intraperitoneal injection and its possible mechanisms.Methods：Sixty-eight SD rats of both males aged 6 weeks weighing220±20g were randomly divided into two groups with 34 rats in each group.Each animal was anesthetized with chloral hydrate by intraperitoneal injection(350mg／kg)．Following anesthesia，caudally based dorsal random patternskin flaps were designed measuring 8cm×2cm dimensions in rats, which wereraised from the deep fascia，then stopped bleeding, sutured back to its originalplace．Each rat in the experimental group was given a intraperitoneal injectionwith simvastatin (5mg/kg) and the control group animals each received thesame volume of saline also by intraperitoneal injection, Once a day for 7 days.The change of morphology were observed every postoperative day. Five daysafter operation, 8 rats were executed in each group，then the skin flap tissueswere got from the near，mid and distal segments(2、4、6 cm from the pedicel ), then producted section and HE dyed, pathological changes were observedwith light microscope. On postoperative day 7, all rats were executed, thesurvival rate of all flaps in the two groups were observed, and 0.5cm×0.5cmsize tissue getting from the near，middle and distal segments of the skin flapwere divided into two parts, one part was made to homogenate and centrifuge,the levels of NOS and ICAM-1 were measured from the extracted skin tissue,immunohistochemical test was performed to detect the microvessel density(MVD) in the other part.Results：The data shows that：No l：Five days after operation, the pathological figure of the tissuessuggest that in the experimental group tissue the dropsy and inflammatory cellinfiltration is slighter than that in the control group．No 2：On postoperative day 7，the mean percentages of flap survivalsof rats in two groups were 62.44±5.05 and 46.87±6.02 percent，respectively.That tell us the flap survival rate in experimental group was remarkablyhigher than that in control group（P<0.05）.No 3：Seven days after operation，the MVD of the middle segment ofthe flap and the NOS level of every equal segment were greater（P<0.05）inthe experimental group than that in the control group, meanwhile the ICAM-1levels remarkably lower than that in the control group (P<0.05)．Conclusion：Simvastatin can increase the survival rate of random skinflaps in rats, which may be related to that simvastatin can improve endothelialfunction directly, promote angiogenesis, increase NOS and restrain theexpression of ICAM-1, thereby reducing inflammatory responses.