| PURPOSE:To study the effect of topical application of VEGFR inhibitor PTK787 on the regulation of angiogenic related factors during bone healing process, as well to evaluate the effect of angiogenesis on neurogenesisMETHODS: 32 male adult Sprague-Dawley(SD) rats were randomly divided into 4groups. Two 5mm diameter critical bone defects were symmetrically created on the parietal bone. The right side bone defect was administrated with13.125 mg PTK787,while the left side was administrated the solutions without PTK787 via osmotic pump over 7 days with a releasing rate of 1ul/h.Rats were euthanized at 3、7、14、and 28 days after surgery. The effect of PTK787 on angiogenesis was assessed by immunohistochemical staining of VEGF、VEGFR-2、CD34 and the numbers of blood vessels.In addition, the neuronal differentiation marker β III-tubulin in bone defect area was determined with immunohistochemical assay during different bone healing phase to investigate the of PTK787 on neurogenesis.RESULTS: The expression of CD34 was higher in control groups compared to PTK787 administrated groups at each time point, with significantly differences at 7 and 14 days.Even though the number of blood vessels showed no significant differences between the PTK787 group and the control group at all time points, the number of blood vessels in PTK787 administrated group was lower than the control group. The expression of VEGF was higher in control groups compared to PTK787 administrated at 7、14 and 28 days, with significant differences at 7 and 14 days. The expression of VEGFR2 was significant higher in control group compared to the PTK787 administrated group at 3、14 and 28 days(P<0.05). The expression of β-III tublin was higher in control group compared to PTK787 adminstrated group at all time points, with significant differences at 3 days.CONCLUSION: It was concluded from this study that the VEGFR inhibitor PTK787 could inhibit the process of angiogenesis during the bone healing process, through down- expression of VEGF/VEGFR-2. In addition, the presence of PTK787 may modulate neurogenesis through inhibit angiogenesis. |
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