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外源性神经生长因子对兔下颌骨骨折伴局部神经损伤愈合过程中 BMP-9 和 VEGF 表达的影响。

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.

机构信息

Oral Maxillofacial Trauma and Orthognathic Surgery, Affiliated Stomatological Hospital of Zunyi Medical University, Zunyi, Guizhou, China.

出版信息

J Orthop Surg Res. 2021 Jan 21;16(1):74. doi: 10.1186/s13018-021-02220-z.

Abstract

BACKGROUND

Mandibular fracture healing is a complex process involving nerves and growth factors. Nerve growth factor (NGF) not only facilitates the maintenance of sympathetic neurite growth but also stimulates other growth factors that can promote the essential osteogenesis and angiogenesis for fracture healing. Therefore, it is necessary to analyze the combined effects of NGF, bone morphogenic protein-9 (BMP-9), and vascular endothelial growth factor (VEGF) to accelerate the healing of mandible fractures.

METHODS

The models of mandible fracture with local nerve injury established in 48 rabbits were randomly divided into nerve growth factor group (NGF group), gelatin sponge group (GS group), blank group, and intact group. The recovery of nerve reflex was assessed by observing the number of rabbits with lower lip responses to acupuncture. The fracture healing was observed with visual and CBCT, and then callus tissues from the mandibular fracture area were collected for hematoxylin and eosin (HE) staining observation, and the expression of BMP-9 and VEGF in callus at different stages was detected by quantitative real-time PCR (qRT-PCR).

RESULTS

Needling reaction in the lower lip showed the number of animals with nerve reflex recovery was significantly higher in the NGF group than that in the GS and blank groups at the 2nd and 4th weeks after the operation. The combined results of macroscopic observation, CBCT examination, and histological analysis showed that a large number of osteoblasts and some vascular endothelial cells were found around the trabecular bone in the NGF group and the amount of callus formation and reconstruction was better than that in the GS group at the 2nd week after the operation. The qRT-PCR results indicated that the expression levels of BMP-9 and VEGF in the four groups reached the highest values at the 2nd week, while the expression levels of both in the NGF group were significantly higher than that in the GS group.

CONCLUSION

The exogenous NGF could accelerate the healing of mandible fractures. This work will provide a new foundation and theoretical basis for clarifying the mechanism of fracture healing, thereby promoting fracture healing and reducing the disability rate of patients.

摘要

背景

下颌骨骨折愈合是一个涉及神经和生长因子的复杂过程。神经生长因子(NGF)不仅有利于维持交感神经轴突的生长,而且还刺激其他生长因子,这些生长因子可以促进骨折愈合所必需的成骨和血管生成。因此,有必要分析 NGF、骨形态发生蛋白-9(BMP-9)和血管内皮生长因子(VEGF)的联合作用,以加速下颌骨骨折的愈合。

方法

48 只兔下颌骨局部神经损伤骨折模型随机分为神经生长因子组(NGF 组)、明胶海绵组(GS 组)、空白组和完整组。通过观察针刺下唇反应的兔子数量评估神经反射的恢复情况。通过肉眼观察和 CBCT 观察骨折愈合情况,然后采集下颌骨骨折区的骨痂组织进行苏木精-伊红(HE)染色观察,并通过定量实时 PCR(qRT-PCR)检测不同阶段骨痂中 BMP-9 和 VEGF 的表达。

结果

下唇针刺反应显示,术后第 2、4 周,NGF 组动物神经反射恢复的数量明显高于 GS 组和空白组。宏观观察、CBCT 检查和组织学分析的综合结果表明,NGF 组在术后第 2 周,大量成骨细胞和一些血管内皮细胞出现在小梁骨周围,骨痂形成和重建的量明显好于 GS 组。qRT-PCR 结果表明,四组 BMP-9 和 VEGF 的表达水平在第 2 周达到最高值,而 NGF 组的表达水平明显高于 GS 组。

结论

外源性 NGF 可加速下颌骨骨折愈合。这项工作将为阐明骨折愈合机制提供新的基础和理论依据,从而促进骨折愈合,降低患者的残疾率。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d5ea/7818757/dbd2cf98456a/13018_2021_2220_Fig1_HTML.jpg

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