中国神经再生研究(英文版)

中国神经再生研究(英文版) ›› 2018, Vol. 13 ›› Issue (3): 484-491.doi: 10.4103/1673-5374.228732

• 原著:周围神经损伤修复保护与再生 • 上一篇    下一篇

乳香提取物AKBA促进许旺细胞增殖及损伤坐骨神经功能的恢复

  

  • 收稿日期:2018-01-15 出版日期:2018-03-15 发布日期:2018-03-15

Acetyl-11-keto-β-boswellic acid extracted from Boswellia serrata promotes Schwann cell proliferation and sciatic nerve function recovery

Xiao-wen Jiang, Bin-qing Zhang, Lu Qiao, Lin Liu, Xue-wei Wang, Wen-hui Yu   

  1. Department of Veterinary Medicine, Northeast Agricultural University, Harbin, Helongjiang Province, China
  • Received:2018-01-15 Online:2018-03-15 Published:2018-03-15
  • Contact: Wen-hui Yu,yuwenhui@neau.edu.cn.

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摘要：

乳香具有促进血液循环和组织再生的作用，AKBA是从乳香中提取的一种具有抗炎性能的小分子。作者假设其具有促进损伤坐骨神经再生的作用。为验证此假设，实验首先以神经夹持方法建立坐骨神经损伤大鼠模型，在损伤后第1天开始通过腹腔注射给予1.5，3，6mg/kg AKBA，每2d一次，连续干预30d。以坐骨神经指数评价大鼠损伤坐骨神经功能，以小腿三头肌Cuadros指数评价肌萎缩程度，以苏木精-伊红染色观察损伤神经病理变化，以Western blot分析检测损伤神经中P-ERK1/2表达水平，以免疫组化检测损伤神经中S100免疫荧光反应。体内实验结果显示3，6mg/kg AKBA能显著提升坐骨神经损伤大鼠坐骨神经指数、小腿三头肌Cuadros指数、损伤侧神经中P-ERK1/2水平以及S100免疫阳性反应，并改善损伤侧神经病理表现；体外实验以0-20µg/mL AKBA对许旺细胞进行干预，以CCK-8检测许旺细胞的增殖情况，结果显示2 µg/mL时是其最佳的治疗浓度，且2 µg/mLAKBA干预后细胞中P-ERK1/2表达水平随时间的延长而增加。当培养体系中加入ERK1/2抑制剂PD98059（2.5 μL/mL）时，AKBA对许旺细胞中P-ERK1/2表达的诱导作用被部分抑制，结果说明AKBA能够促进损伤的周围神经再生，而ERK是这一过程的关键蛋白。

orcid:0000-0002-3744-4575(Wen-hui Yu)

 

关键词: 神经再生, AKBA, 周围神经损伤, 坐骨神经, 许旺细胞, 细胞增殖, ERK信号通路, PD98059

Abstract:

Frankincense can promote blood circulation. Acetyl-11-keto-β-boswellic acid (AKBA) is a small molecule with anti-inflammatory properties that is derived from Boswellia serrata. Here, we hypothesized that it may promote regeneration of injured sciatic nerve. To address this hypothesis, we established a rat model of sciatic nerve injury using a nerve clamping method. Rats were administered AKBA once every 2 days at doses of 1.5, 3, and 6 mg/kg by intraperitoneal injection for 30 days from the 1st day after injury. Sciatic nerve function was evaluated using the sciatic functional index. Degree of muscle atrophy was measured using the triceps surae muscle Cuadros index.Neuropathological changes were observed by hematoxylin-eosin staining. Western blot analysis was used to detect expression of phospho-extracellular signal-regulated kinase 1 and 2 (p-ERK1/2) in injured nerve. S100 immunoreactivity in injured nerve was detected by immunohistochemistry. In vivo experiments showed that 3 and 6 mg/kg AKBA significantly increased sciatic nerve index, Cuadros index of triceps muscle, p-ERK1/2 expression, and S100 immunoreactivity in injured sciatic nerve of sciatic nerve injury model rats. Furthermore,for in vitro experiments, Schwann cells were treated with AKBA at 0–20 μg/mL. Proliferation of Schwann cells was detected by Cell Counting Kit-8 colorimetry assay. The results showed that 2 μg/mL AKBA is the optimal therapeutic concentration. In addition, ERK phosphorylation levels increased following 2 μg/mL AKBA treatment. In the presence of the ERK1/2 inhibitor, PD98059 (2.5 μL/mL), the AKBA-induced increase in p-ERK1/2 protein expression was partially abrogated. In conclusion, our study shows that AKBA promotes peripheral nerve regeneration with ERK protein phosphorylation playing a key role in this process.

Key words: nerve regeneration, acetyl-11-keto-β-boswellic acid, peripheral nerve injury repair, sciatic nerve crush injury, Schwann cells, cell proliferation, ERK signaling pathway, PD98059, neural regeneration