Department of Hand Surgery, Yantaishan Hospital, Yantai, China.
Eur Rev Med Pharmacol Sci. 2017 Apr;21(8):1780-1786.
The use of an antibody to block the neurite outgrowth inhibitor Nogo-A has been of great interest for promoting axonal recovery as a treatment for peripheral nerve injuries. The present study aimed to investigate the signaling pathway of p75 neurotrophin receptor (NTR) and Nogo receptor (NgR) in a sciatic nerve transection (SNT) rat model and evaluate the underlining mechanisms.
Seventy-five Sprague-Dawley (SD) rats were randomly divided into 3 groups (n=25), namely the sham group, sciatic nerve transection (model) group and Nogo-A-pAb group. Following euthanasia, spinal cord and sciatic nerve of the operation site were harvested, fixed in formalin. Hematoxylin and eosin (HE) staining was used to evaluate the sciatic nerve pathology. The mRNA and protein expression levels of Nogo-A, NTR were assessed by Real-time polymerase chain reaction (RT-PCR) and Western blotting, respectively.
Histology showed enhanced regeneration of spinal axon in the anti-Nogo-A antibody group. At 48 hours after operation, mRNA of Nogo-A and NTR were higher in model group compared with control group. mRNAs were at their highest levels at 1 week, while these were at normal levels after 4 weeks in Nogo-A-pAb group. The protein levels of Nogo-A and NTR were higher in model group compared with sham-operation group at 1-week after operation; Nogo-A-pAb could reduce these proteins levels.
The results suggested Nogo-A antibody might represent a promising repair strategy to promote recovery following SNT.
使用抗体阻断神经生长抑制因子 Nogo-A 已成为促进轴突恢复的一种有吸引力的方法，可作为治疗周围神经损伤的方法。本研究旨在探讨神经生长因子受体 p75（NTR）和 Nogo 受体（NgR）在坐骨神经横断（SNT）大鼠模型中的信号通路，并评估潜在机制。
75 只 Sprague-Dawley（SD）大鼠随机分为 3 组（n=25），即假手术组、坐骨神经横断（模型）组和 Nogo-A-pAb 组。安乐死后，取手术部位的脊髓和坐骨神经，固定于福尔马林中。苏木精和伊红（HE）染色用于评估坐骨神经病理学。通过实时聚合酶链反应（RT-PCR）和 Western blot 分别评估 Nogo-A、NTR 的 mRNA 和蛋白表达水平。
组织学显示抗 Nogo-A 抗体组脊髓轴突再生增强。术后 48 小时，模型组 Nogo-A 和 NTR 的 mRNA 高于对照组。mRNA 在 1 周时达到最高水平，而在 Nogo-A-pAb 组 4 周后恢复正常水平。术后 1 周，模型组 Nogo-A 和 NTR 的蛋白水平高于假手术组；Nogo-A-pAb 可降低这些蛋白水平。
结果表明，Nogo-A 抗体可能代表一种有前途的修复策略，可促进 SNT 后的恢复。
