Insulin effects on fracture healing and cytokines in the osteotylus in experimental diabetic rats / 中国组织工程研究

ABSTRACT

BACKGROUND:Fracture healing in diabetic patients is usual y unsatisfactory because of hormones and metabolic disorder, and an eventual multiple organ dysfunction resulting from high blood glucose. OBJECTIVE:To dynamical y observe the changes of cytokines during the fracture healing process in diabetic rats before and after insulin treatment. METHODS:A total of 120 Sprague-Dawley rats were included in this study. Of them, 90 rats intravenously injected with 5%tetraoxypyrimidine to induce rat models of diabetes were randomized into insulin treatment and diabetes groups, respectively. The remaining 30 rats were intravenously injected with equal volume of saline and selected as control group. The next day, blood glucose was determined. Healing at 1, 4, and 8 weeks after fracture were observed by the X-ray film. Biomechanical strength of the injured right tibia was measured at 4, 6, and 8 weeks after modeling. Cytokines in the osteotylus were determined by immunohistochemical staining and in situ hybridization technique. RESULTS AND CONCLUSION:The X-ray films showed that the speed of fracture healing in the diabetes group was slower than insulin treatment and control groups. Biomechanical strength of the osteotylus in the diabetes group was significantly decreased compared with the insulin treatment and control groups. However, there were no significant differences in above-mentioned parameters between the control and insulin treatment groups. Bone morphogenetic protein 2, basic fibroblast growth factor, transforming growth factor-beta, and vascular endothelial growth factor were widely expressed in the osteotylus and their expressions in diabetes group were significantly lower and slower than those in the control and insulin treatment groups. There was no statistical difference between control and insulin treatment groups. These results indicate that osteotylus formation speed, biomechanical strength, and growth factor expressions at the fracture site in diabetes rats were decreased compared with normal rats. Insulin treatment can enhance cytokine levels at the fracture site, thereby promoting the osteoblast proliferation and fracture healing.