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重组人神经生长因子(rhNGF-β)基因转导促进大鼠挤压性损伤面神经的再生。

Recombinant human nerve growth factor (rhNGF-β) gene transfer promotes regeneration of crush-injured mental nerve in rats.

机构信息

Department of Oral & Maxillofacial Surgery, School of Dentistry, BinZhou Medical School, Binzhou, China.

出版信息

Oral Surg Oral Med Oral Pathol Oral Radiol. 2012 Mar;113(3):e26-34. doi: 10.1016/j.tripleo.2011.07.002.

Abstract

OBJECTIVE

The aim of this study was to evaluate whether the recombinant human nerve growth factor (rhNGF-β) gene transfer at a crush-injured sensory nerve can enhance nerve regeneration.

STUDY DESIGN

A 4-mm crush injury was made on the mental nerve of mandible in rats, and rhNGF-β adenovirus (6 μL, concentration = 1.0 × 10(11) pfu/μL) was injected at the crushed site for the experimental group (NGF-Ad group, n = 15) and the same volume of PBS for the controls (PBS group, n = 15). A sham group of uninjured nerve was also used for the normal control (Sham group, n = 15). The effect of rhNGF-β adenovirus injection was evaluated by real-time reverse trascriptase polymerase chain reaction for the quantification of nerve growth factor (NGF), low-affinity NGF receptor (p75NTR), and its tyrosine receptor kinase A (trkA) mRNA expression at the trigeminal ganglion (TG) 5 days after injection. Nerve regeneration was evaluated with sensory test, retrograde axonal transport in the TG, and histomorphometric study for 4 weeks.

RESULTS

NGF, p75NTR, and trkA mRNA expression was significantly increased at the TG 5 days after injection of rhNGF-β adenovirus (P < .05). The NGF-Ad group showed improved sensory recovery (P < .05), and the number of retrograde-labeled sensory neurons and soma size of TG were larger compared with the PBS groups (P < .05). Histomorphometrically, the myelinated axon number, myelin thickness, and G-ratio in the NGF-Ad group was also significantly higher than the PBS groups (P < .05).

CONCLUSIONS

Recombinant human nerve growth factor gene transfer promoted regeneration of crush-injured mental nerve.

摘要

目的

本研究旨在评估在挤压损伤感觉神经处转染重组人神经生长因子(rhNGF-β)基因是否能增强神经再生。

设计

在大鼠下颌骨颏神经处造成 4mm 挤压伤,实验组(NGF-Ad 组,n=15)在挤压部位注射 rhNGF-β腺病毒(6μL,浓度=1.0×10(11)pfu/μL),对照组(PBS 组,n=15)注射相同体积的 PBS。另设未损伤神经的假手术组作为正常对照(Sham 组,n=15)。转染 rhNGF-β 腺病毒 5 天后,通过实时逆转录聚合酶链反应检测三叉神经节(TG)中神经生长因子(NGF)、低亲和力 NGF 受体(p75NTR)及其酪氨酸受体激酶 A(trkA)mRNA 的表达,评估 rhNGF-β 腺病毒注射的效果。4 周后通过感觉测试、TG 逆行轴突运输和组织形态计量学研究评估神经再生情况。

结果

rhNGF-β 腺病毒注射后 5 天,TG 中 NGF、p75NTR 和 trkA mRNA 表达显著增加(P<0.05)。NGF-Ad 组感觉恢复改善(P<0.05),逆行标记的感觉神经元数量和 TG 体大小均大于 PBS 组(P<0.05)。组织形态计量学显示,NGF-Ad 组有髓神经轴突数量、髓鞘厚度和 G 比值也显著高于 PBS 组(P<0.05)。

结论

重组人神经生长因子基因转染促进挤压损伤颏神经再生。

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