The Influences Of PTH On High-fat Diet-fed With Streptozotocin-treated And Ovariectomized Rats Closed Fracture Healing

Objectives Objective: To investigate the effects of parathyroid hormone on fracture healing in high fat diet and STZ-induced diabetic ovariectomized rats.Methods 50 SPF-grade 2-month-old female SD rats were housed to adapt the environment for 7 days, then the animals were randomly divided into 5 groups(10 for each group): F+Sham group, F +OVX group, F+Sham+STZ group, F+STZ+OVX group,F+OVX+STZ+PTH group. At week 0, Sham+F group and OVX+F group were supplied with standard diet, and the other three groups were supplied with high fat diet during the experiment. At week 3, STZ+F group, F+STZ+OVX group, and F+OVX+STZ+PTH group were intraperitoneal injected STZ(35mg/kg), and the other two group were injected placebo. At week 4, sham operation were performed on the animals in Sham+F group, and the other four groups were performed ovariectomy. At week 10, the right femur of all the animals were closed fractured by the impact on the mid-shaft, then the fractures were fixed.The X-ray evaluations were performed immediately after fixation. The F+OVX+STZ+PTH group was treated by PTH(1-34)(50?g/kg, 5 days per week), and the F+STZ+OVX group was teated by normal saline. All the animals were sacrificed at week13, and the right femurs were evaluated again by X-ray. Callus area for each animals was evaluated by Image J, histological evaluation was performed by Safrinin O/fast green staining, and the expression of VEGF were evaluated by immunohistochemistry.Results 1 The results of X-ray showed the edges of fracture were completely disappeared in Sham+F group, periosteal reaction density approximate bone shadow, Bone defect is filled by bone callus. And the bone mineral density of bone callus was similar with that of cortical.The group of F+STZ,F+OVX and F+OVX+STZ were not observed callus formation at the edges of fracture,but healing tissue. The increase of the number of callus tissue cells were found in the fracture end of F+OVX+STZ+PTH group, meanwhile the trabecular bone bridge formed in the fracture tissue at the edges of fracture.the X-ray grading score of fumer fracture in Sham+F group was higher than that of the other groups(P<0.05). the X-ray grading score of fumer fracture in F+OVX+STZ+PTH group was higher than that of F+OVX+STZ+PTH group(P<0.05).2 The results of bone callus area showed that the group of F+sham was higher than F+STZ,and STZ +OVX+F group(P<0.05).the bone callus area of OVX+F group was lower than that of F+STZ+OVX group(P<0.05). 3 Immunohistochemical statining demostrated that PTH increased the expression of VEGF in the callus than that of F+STZ+OVX group(P<0.05). The expression of VEGF in F+OVX and F+STZ group were lower than that of F+Sham group(P<0.05).Conclusions 1 The closed fractures stump of high-fat diet Streptozotocin inducing and Ovariectomized rats delayed healing.2 PTH therapy can promote stump closed fracture healing of the High-fat diet Streptozotocin inducing and ovariectomized rats,which may be related to the upregulation of VEGF expression levels in callus.3...