The Contrast Study Of Biphosphate, Simvastatin Promote The Healing Of Mandibular Fractures In Diabetic Rats

Objectives By establishing diabetes type I Wistar animal models of mandibular fractures objectively, observing the mandible fracture healing process in diabetic rats after application of alendronate and simvastatin, determining separately the OPG,BGP serum contents and the immunohistochemical expression in the callus area, to explore, in the diabetic state, the effects of alendronate and simvastatin on fracture healing process and provide experimental evidence for the selection of clinical diabetes drugs to promote bone healing.Methods 120 male Wistar rats, 6~8 weeks old, weighing 250~300g, were randomly divided into five groups: control group(Group A), diabetic fracture group(Group B),diabetic fracture+insulin-treated group(Group C), diabetic fracture+insulin+alendronate group(Group D), diabetic fracture+insulin+simvastatin(Group E). After two weeks of adaptation feeding, except for the control group, the four other with intraperitoneal injection of STZ, were formed an animal model of type I diabetes. Three days later, the determination of random blood glucose levels, blood glucose≥16.7mmol / L rats, which was deemed successful model. After the successful establishment of a stable model of diabetes, all the rats were surgically established unilateral mandibular fracture model.The next day, the 8-week drug intervention began. Group A(control group): daily isovolumetric saline gavage; Group B(diabetic group): daily isovolumetric saline gavage;Group C(insulin group): daily 3UI(units) subcutaneous injection of insulin, and is ovolumetric normal saline; Group D(insulin+alendronate treatment group): daily given3UI(units) of insulin injections, with a 5mg/kg orally alendronate solution.Group E(insulin+simvastatin treatment group): daily given 3UI(units) of insulin injections, with a 10mg/kg orally simvastatin solution. After the surgery, six rats out of each group were sacrificed randomly every two weeks(2, 4, 6, 8w), determining serum OPG, BGP content by ELISA. At the same time, remove the mandible, shoot X-ray,observe the fracture healing and test bone density. Then make paraffin samples, HEstaining, immunohistochemical examination of callus area OPG, BGP expression.Results 1 128 Wistar animals were eexperimented with, 8 of which were dead in the diabetic model-establishing process, but none of them died in the model-establishing process of diabetic fractures.So 8 Wistars were get rid of in all and replenished. The successful rate of model-establishment was 92.3%. 2 The results of X-ray combined with bone density comparison shows: within two weeks, each group’s fracture line was clear,of the fracture line density was lower, and no significant callus growth was seen. The differences between compared groups was not statistically significant(P>0.05). In 4weeks, in Group A, C, D, E the fracture line was blurred, and the callus growth could be seen. Group A and Group D grow more; the fracture line is still clearly seen in Group B.Between Group A and the other four groups, there are significant differences(P<0.05),and there are also significant differences(P<0.05) between Group D and Group B, C, and E. In 6w, 8w, In group A, D and E, the fracture density was relatively high, the fracture line blurred, respectively compared with Group B and Group C, the differences were statistically significant(P<0.05). 3 OPG expression: Group A in 2,4,6,8 weeks were significantly different from Group B(P<0.05), indicating that the OPG expression reduces after the diabetic fracture in Group B; In 2 weeks, compare the positive expression of Group D and E with Group B and C, the difference was statistically significant(P<0.05), which is slightly lower than Group A, with no statistical significance. 4 BGP expression: In 2 weeks, cpmpared with Group B,positive expression was a little stronger in Group A,C and E(P<0.05),mostly spread in osteoblast cytoplasm.In 4 weeks, BGP expressions were stronger in Group A,C,D and E; and that in Group D and E were higher than that in Group B and C(P<0.05); BGP in the callus areas expressed most strongly in all the groups in the fracture healing process, afterwards it decreased gradually.In 6 weeks,the expressions in Group D and E were still higher than Group B and C(P<0.05), the difference was statistically significant. In 8 weeks, the comparison of BGP concentrations in Group A, C, D and E was not statistically significant..Conclusions The experiment indicated that: 1 Fracture healing of the diabetic group was the worst,the insulin-treated group was evidently better than the diabetic fracture group,so diabetes can lead to delayed fracture healing. 2 Alendronate can efectively increase the BMD in the callus area in the early diabetic fracture healing process,Alendronate and simvastatin can both increase the cell content of OPG and BGP in the fracture areas though they affected the bone metabolite differently. Both of them can promote bone healing to different degrees.