| Objective:In this study,we designed different doses of Attovastatin to gavage rats to observe their effect on the survival area and pathological changes of extra long random skin flap of rats.The expression of VEGF/bFGF,the content of SOD/NO/MDA and the number of neovascularization in the flap were detected.And the mechanism of the results was preliminarily discussed in order to provide reliable experimental basis for its wider clinical application.Methods:Sixty healthy SD rats were selected and randomly numbered and divided into 5 groups(n=12).The control group included(P10?P20?P30?P40)and the P group is a negative control group.the rats were given intragastric administrations from 3 days before operation to 3 days after operation at the same time everyday.Use mark pen on the back of rats to design intercrestal line as the pedicle and the posterior midline axis of the 8cm×2cm(The ratio of length to width is 4:1)the extra long random skin flap on the back.On the second day after operation,6 rats in each group were randomly selected.The tissue mass of 1.5 cm x 1.5 cm thick flap was taken from the middle segment of the flap,and the contents of SOD,NO and MDA were detected by ELISA method.On the 7~thh day after operation,the remaining rats in each group were killed,and the same size and thickness tissue mass was taken from the middle part of the flap,and they were divided into two parts:one was used to detect the expression of VEGF and b FGF by PCR,the other was stained with HE and immunohistochemistry.Histopathological changes and microvessel count were observed.Results:1.The general observation:In the P control group,only a few of the proximal skin flaps survived,and the middle and distal segments were severely necrotic.In P10 group,the color of the proximal segment of the skin flap was ruddy and warm.The color of the distal part of the flap gradually darkened and reddish brown,and the elasticity was poor.There was no bleeding in the acupuncture.And the distal segment was dark brown and part of the necrotic part was covered with black scab shell.The survival rate of skin flap in P20 group was better than that in P10group and P group.The color,skin temperature and elasticity of the survived skin flap were similar to those of normal tissue,and hair growth could be seen.The survival area of the skin flap in P30 group was slightly larger than that in P40 group.The proximal and middle segments of the skin flap in both groups survivedshowing reddish color,hair growth and clinging to the base.Only a few black necrotic areas were found at the margin of the distal incision.2.Flap survival rate:P group(39.81±2.28)%,P10 group is(49.77±4.78)%,P20 group is(59.64±2.41)%,P30 group is(78.05±1.79)%,P40 group is(70.54±4.36)%,The experimental groups were compared with the control group P<0.01,the difference was statistically significant,That is to say,the survival rate of skin flap could be improved by taking Atto vastatin orally,and there were significant differences in the survival area of flap in different dosage groups.3.Laboratory results3.1 Results of HE staining:In group P,tissue edema,disordered tissue structure,diffuse infiltration of a large number of inflammatory cells and absence of epidermis were found.In P10 group,the collagen fibers in the dermis became thinner and looser,a few plasma cells infiltrated in the superficial dermis.In the P20 group,a case of cortical necrosis and disintegrating tissue structure was observed.Occasionally,necrosis of subcutaneous tissue and necrosis area showed homogenized red-stained protein-like substance and a large number of proliferative fibrous tissue.In P30 group,a few inflammatory cells were infiltrated,the structure of skin epidermis and dermis was intact,the boundary was clear,the connective tissue and collagen fibers were arranged neatly.In P40 group,there were 4cases with intact skin structure and no obvious lesion.Focal necrosis of epidermal tissue,accumulation of inflammatory cells,atrophy of epidermal cells and decrease of layer number were found in 2 cases of P40 group.3.2 Expression of CD31 in tissue microvessels:Group P:6.53±1.30(stripe/view),Group P10:7.60±1.61(stripe/view),P40:12.46±2.73(stripe/view).Univariate analysis of variance showed that there was significant difference in microvessel density between P10,P20,P30 and P40 compared with P group(P<0.05).3.3 Expression of RNA of VEGF and b FGF in tissues:The expression of VEGF and bFGF in the tissues of each drug group was up-regulated by different times as compared with that in group P.the trend was basically the same.The results obtained from VEGF and bFGF were analyzed and obtained that P<0.05,indicating that the differences among the groups were statistically significant.There was no significant difference between P10 group and P20group(P>0.05).3.4 Contents of SOD,NO and MDA in tissue proteins:The SOD content in Atovastain intervention group was significantly higher than that in P group,P<0.01,and the difference was statistically significant.No content:There was no significant difference between P40 group and P20 group(P>0.05).The content of MDA:There was no significant difference between P10 group and P group(P>0.05).Conclusion:Atorvastatin can effectively improve the survival of rat dorsal random flap.The 30mg group was the best in different dosage,that is there was a dose-dependent relationship between the survival rate of the flap and the dosage of the drug.The possible mechanism is that atorvastatin can promote the formation of new blood vessels,reduce ischemia reperfusion injury and avoid the occurrence of excessive inflammatory reaction. |
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