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补骨脂总黄酮及其活性成分可保护周围神经免受紫杉醇或神经挤压所致的损伤。

Bogijetong decoction and its active herbal components protect the peripheral nerve from damage caused by taxol or nerve crush.

作者信息

Ahn So Hyun, Chang In Ae, Kim Ki-Joong, Kim Chul-Jung, Namgung Uk, Cho Chung-Sik

机构信息

Department of Oriental Medicine, Daejeon University, Daejeon, 300-716, South Korea.

出版信息

BMC Complement Altern Med. 2016 Oct 22;16(1):402. doi: 10.1186/s12906-016-1391-7.

Abstract

BACKGROUND

Bogijetong decoction (BGJTD) is a herbal drug formulation used in the traditional Asian medicine to treat neuropathic insults associated with diabetes and anticancer therapy. To understand the biological basis of BGJTD on protective effects against neuropathy, we investigated physiological and biochemical responses of the sciatic nerves deranged by taxol injection or crush injury in the rats.

METHODS

Dissociated Schwann cells and neurons were prepared from the sciatic nerve and dorsal root ganglia (DRG) respectively and were treated with taxol and BGJTD. The sciatic nerve in the rat was injected with taxol or given crush injury. Animals were then administered orally with BGJTD. Effects of BGJTD treatment on cultured cells and in vivo sciatic nerves and DRG tissues were examined by immunofluorescence staining and western blot analysis. Sciatic nerve regeneration was assessed by histological observation using retrograde tracing technique and by behavioral hot plate test. Eighteen different herbal components of BGJTD were divided into 4 subgroups and were used to select herbal drugs that enhanced neurite outgrowth in cultured neurons.

RESULTS

Morphological abnormalities in the sciatic nerve axons and DRG tissue caused by taxol injection were largely improved by BGJTD treatment. BGJTD treatment enhanced neurite outgrowth in cultured DRG neurons and improved Schwann cell survival. Phospho-Erk1/2 levels were elevated by BGJTD administration in the injured- or taxol-injected sciatic nerves. Vimentin phosphorylation catalyzed by cell division cycle 2 (Cdc2) kinase was induced from Schwann cells in the sciatic nerves after taxol injection and crush injury, and phospho-vimentin levels were further upregulated by BGJTD treatment. Retrograde tracing of DiI-labeled DRG sensory neurons revealed growth-promoting activity of BGJTD on axonal regeneration. A drug group (Be) composed of 4 active herbal components which were selected by neurite growth-enhancing activity was as effective as BGJDT for the recovery of thermal sensitivity of the hind paws which had been suppressed by taxol administration.

CONCLUSIONS

These data suggest that BGJTD and its active herbal components may protects the peripheral nerve from damage caused by taxol injection and nerve crush.

摘要

背景

补骨脂通痹汤(BGJTD)是一种用于亚洲传统医学治疗与糖尿病及抗癌治疗相关的神经病变损伤的草药配方。为了解BGJTD对神经病变保护作用的生物学基础,我们研究了紫杉醇注射或挤压损伤诱导的大鼠坐骨神经的生理和生化反应。

方法

分别从坐骨神经和背根神经节(DRG)制备解离的施万细胞和神经元,并用紫杉醇和BGJTD处理。对大鼠坐骨神经注射紫杉醇或进行挤压损伤。然后给动物口服BGJTD。通过免疫荧光染色和蛋白质免疫印迹分析检测BGJTD处理对培养细胞以及体内坐骨神经和DRG组织的影响。使用逆行追踪技术通过组织学观察和行为热板试验评估坐骨神经再生。将BGJTD的18种不同草药成分分为4个亚组,用于筛选增强培养神经元中神经突生长的草药。

结果

BGJTD处理在很大程度上改善了紫杉醇注射引起的坐骨神经轴突和DRG组织的形态学异常。BGJTD处理增强了培养的DRG神经元中的神经突生长,并改善了施万细胞存活。在受损或注射紫杉醇的坐骨神经中,BGJTD给药可提高磷酸化细胞外信号调节激酶1/2(Phospho-Erk1/2)水平。紫杉醇注射和挤压损伤后,坐骨神经中的施万细胞诱导了由细胞分裂周期2(Cdc2)激酶催化的波形蛋白磷酸化,BGJTD处理进一步上调了磷酸化波形蛋白水平。对DiI标记的DRG感觉神经元的逆行追踪显示BGJTD对轴突再生具有促生长活性。由4种通过增强神经突生长活性筛选出的活性草药成分组成的药物组(Be)在恢复被紫杉醇抑制的后爪热敏感性方面与BGJDT同样有效。

结论

这些数据表明,BGJTD及其活性草药成分可能保护周围神经免受紫杉醇注射和神经挤压所造成的损伤。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/08b5/5075155/1e74fc590d4d/12906_2016_1391_Fig1_HTML.jpg

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