Effects Of Exogenous Nerve Growth Factor On The Expression Of BMP-9 And VEGF In The Healing Of Rabbit Mandible Fracture With Local Nerve Injury

Objective: The aim of this study was to explore the molecular mechanism that Exogenous nervegrowth factor(NGF)promotes the healing of mandibular fracture with neurovascular bundle injury by observing the osteogenesis phenomenon and the expression of Bone morphogenetic protein9(BMP-9)and vascularendothelial growth factors(VEGF)inrabbit model.Methods: Forty-eight New Zealand white rabbits were randomly divided into four groups(N =12),namely the NGF group,the gelatin sponge group(GS group),the blank group and the intact group.In all animals,incomplete fractures(about 5mm×2mm)were made in front of the mental foramen of the mandible through the buccal and lingual.The NGF group cut off the neurovascular bundle and implanted NGF with gelatin sponge as the carrier.The GS group cut off the neurovascular bundle and implanted normal saline with gelatin sponge as the carrier.The blank group cut off the neurovascular bundle without implanting material.The intact group retained the neurovascular bundle intact.Three rabbits were sacrificed in each group for visual inspection,taking X-ray,HE staining and detecting the expression of BMP-9 and VEGF by Real Time Q-PCR,At weeks 2,4,6,and 8.Results: 1.Visual inspection in fracture area:Atweek 4,the fracturelines of the NGFgroup and the intact group were not obvious,while the fractures of the GS group and the blank group showed obvious fibrous callus.At week 6,the fracture lines of the NGF group and the intact group were fused to the surrounding bone,while the fractures of the GS group and the blank group were still distinguishable from the surrounding bone.The adhesion healing of the fractured neurovascular bundle in the NGF group can begin as early as the 2nd week,which is significantly fasterthan that intheGS group and the blank group.2.X-ray photograph: At week 4,the NGF group and the intact group had a higher degree of calcification in the fracture area than the GS and blank groups.At week 6,the fracture line of the NGF group and the intact group was not obvious,while the GS group and the blank group were relatively obvious.3.HE staining: At week 2 and 4,callus reconstruction between the NGF group and the intact group was more regular and uniform than that between the GS group and the blank group in terms of bone trabecular alignment and collagen remodeling.At week 6,the osteogenesis in the NGF group and intact group gradually decreased,and callus reconstruction tended to be completed.But the GS group and blank group were still active in callus reconstruction.At week 8,callus reconstruction was similarto normal bonetissue inall groups.4.Real Time Q-PCR: In the 4 periods,the expressions of BMP-9 and VEGF in eachgroup peaked at the 2th week.The expressions of BMP-9 and VEGF in the NGF group were significantly higher than those in the GS group(P<0.05).The expressions of BMP-9 and VEGF in the intact group weresignificantly higherthan those in the blank group(P<0.05).Andthe GS group was similar to the blank group without statistical significance.After that,the expressions of BMP-9 and VEGF in each group gradually decreased with time.The expressions of BMP-9 and VEGF in the intact group were still higher than those in the blank group at the 4th,6th,and 8th weeks(P<0.05).The expressions of BMP-9 and VEGF in the NGF group were also higher than those inthe GS group at the 4th and 6th week.Among them,the expression of BMP-9 was statistically significant.Conclusion: The exogenous NGFcanpromotethehighexpressions of BMP-9and VEGFin the early stage of mandibular fracture healing after neurovascular injury.This may be one of the molecular mechanisms of exogenous NGFto promotemandibular fracturehealing.