| ObjectiveBy establishing the free flap model of from abdomen transferred to neck in rats,the survival rate of the flap and the contents of SOD,MDA,IL-6 and TNF-α were detected,and the histological observation and analysis of the flap were carried out to study the effect of metformin on the ischemia-reperfusion injury of free flap,and then to explore its possible mechanism,so as to provide a new idea for improving the survival rate of free flap in clinic.MethodNinety female Sprague Dawley(SD)rats of SPF grade were randomly divided into 3 groups:(1)Sham group,(n=30),the skin flap was raised,there was no ischemia in the vascular pedicle,no other treatment was done,and sutured in situ.(2)In the ischemia-reperfusion group(IR group,n=30),a 2cm*3cm-sized skin flap was designed in the left lower abdomen,and the abdominal flap was transplanted to the neck.(3)Metformin group(IR,n=30),the operation was the same as the IR group;4 hours before operation,metformin of 300mg/Kg was injected intraperitoneally in the Met group,and 0.9%normal saline of the same dose was injected in the IR group.The contents of MDA,SOD,IL-6 and TNF-α were measured in Met group and IR group at ischemia 3 0min(After the vascular pedicle of the donor area is completely severed),1 hour after reperfusion and 6 hour after reperfusion(the sampling time of Sham group was the same as that of Met group and IR group).The survival of the flap was observed every day after surgery for a week,and the flap tissues of the 7th day after surgery were observed histologically.Results① Visual observation,7 days after surgery,there was almost no necrotic area in the sham group,the color of the flap was the same as that of the normal skin,and the flap temperature and texture were normal,and there was no obvious inflammatory secretion when the flap was lifted.The survival area of the flap in the Met group was smaller than that in the Sham group,the edema was mild,the color,temperature and texture of the flap were normal,and there were inflammatory secretions only in the distal area of the flap.The survival area of the flap in the IR group was smaller than that in the Met group,the distal flap was dark brown,the flap temperature was lower than that of the normal skin,the texture is inelastic,and there are more inflammatory secretions in the lift flaps.②the survival rate of the flaps,Sham group>Met group>IR group,there is significant difference among the three groups(P<0.05).③HE staining of flap tissue,7 days after surgery,a large number of leukocyte infiltration and more fibroblasts could be seen in the tissue space of IR group,while less leukocyte infiltration and intact tissue structure of flap could be seen in Met group and Sham group.④ The results of biochemical detection of SOD and MDA.The content of MDA in IR group>Met group>Sham group at ischemia 30min,1 hour after reperfusion and 6 hour after reperfusion there was statistical difference between any two groups(P<0 05);and the content of SOD in Sham group>Met group>IR group at 30min after ischemia,1 hour after reperfusion and 6 hour after reperfusion and there was significant difference between any two groups(P<0 05).⑤The results of IL-6 and TNF-α detected by elisa showed that the contents of IL-6 and TNF-α in tissue were IR group>Met group>Sham group after ischemia 30min and reperfusion for 1 hour,and there was significant difference between any two groups(P<0.05);On the 6 hour after reperfusion,the content of IL-6,IR group>Met group>Sham group,there was significant difference between IR group and Met group(P<0.05),there was no significant difference between Sham group and Met group(P>0.05);On the 6 hour after reperfusion,there was almost not expressed of TNF-α in the Sham group,and TNF-αin IR group was higher than that in Met group,and there was a significant difference(P<0.05).ConclusionMetformin can improve the survival rate of free flaps.The histological observation of the free flaps of rats treated with metformin showed that the inflammatory reaction was alleviated,Metformin directly or indirectly scavenges oxygen free radicals,inhibits lipid peroxidation,reduces the production of cellular inflammatory factors,and reduces the flap ischemia-reperfusion damage. |