The Effects Of Insulin Therapy On Fracture Healing And Expression Of VEGF In Experimental Diabetic Rats

ObjectiveTo investigate effects of diabetes mellitus on rat fracture healing after intervention treatment of application of insulin and its mechanism by molecular, cellular methods.MethodsA total of 198 male Wister rats were randomly divided into Diabetes insulin treatment group (n=66), non-treatment group(n=66) and control group(n=66). Diabetic rats model were made by injection alloxan into their abdominal cavities. Whereas, the control group was treated with equivalent sterilized saline. Then a fracture model was made on tibia by surgical methods and allowed to heal. X-ray evaluation were performed in the three groups after 1th,2th,4th,6th,8th weeks. Four animals from each group were killed respectively at third day,1th, 2th, 4th, 6th, 8th week after fracture and the fractured tibia bone were processed undecalcified for histological and immunohistochemical studies. Expression intensity of VEGF was evaluated by microscopy at different times. Biomechanical test were undergone at 4th, 6th and 8th week..ResultsRadiographs study showed that: there were a more severe periosteal reaction and a more rapid cortical reconstruction in control and treatment groups versus diabetic animals. Biomechanical analysis showed mechanical strength of the affected tibia was more weaker in diabetic animals than both control and insulin intervention treatment groups. Histologically, there was a delay in chondrocyte maturation and hypertrophy seen in diabetic tibia. Immunohistochemical staining demonstrated that endogenous VEGF was widely distributed on fracture site at 1th and 3th week in control and treatment rats. Otherwise, VEGF was much less in the callus and periosteum of diabetic rats.ConclusionThe experimental results show that diabetic mellitus significantly affects the callus formation and reducing VEGF expression at the site of bone fracture. Insulin therapy could improve their expression significantly. Therefore , the fracture healing of diabetes rats may be affected by reducing the synthesis of cytokines at fracture site. Insulin therapy may improve fracture healing by affecting cytokine expression at the fracture site.