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埃坡霉素B对脊髓损伤后瘢痕形成抑制作用的机制

Mechanisms responsible for the inhibitory effects of epothilone B on scar formation after spinal cord injury.

作者信息

Zhao Wei, Chai Yong, Hou Yun, Wang Da-Wei, Xing Jian-Qiang, Yang Cheng, Fang Qing-Min

机构信息

Department of Spinal Surgery, Binzhou Medical University Hospital, Binzhou, Shandong Province, China.

Department of Anatomy, Binzhou Medical University, Yantai, Shandong Province, China.

出版信息

Neural Regen Res. 2017 Mar;12(3):478-485. doi: 10.4103/1673-5374.202921.

DOI:10.4103/1673-5374.202921
PMID:28469665
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5399728/
Abstract

Scar formation after spinal cord injury is regarded as an obstacle to axonal regeneration and functional recovery. Epothilone B provides moderate microtubule stabilization and is mainly used for anti-tumor therapy. It also reduces scar tissue formation and promotes axonal regeneration after spinal cord injury. The aim of the present study was to investigate the effect and mechanism of the microtubule-stabilizing reagent epothilone B in decreasing fibrotic scarring through its action on pericytes after spinal cord injury. A rat model of spinal cord injury was established dorsal complete transection at the T10 vertebra. The rats received an intraperitoneal injection of epothilone B (0.75 mg/kg) at 1 and 15 days post-injury in the epothilone B group or normal saline in the vehicle group. Neuron-glial antigen 2, platelet-derived growth factor receptor β, and fibronectin protein expression were dramatically lower in the epothilone B group than in the vehicle group, but β-tubulin protein expression was greater. Glial fibrillary acidic protein at the injury site was not affected by epothilone B treatment. The Basso, Beattie, and Bresnahan locomotor scores were significantly higher in the epothilone B group than in the vehicle group. The results of this study demonstrated that epothilone B reduced the number of pericytes, inhibited extracellular matrix formation, and suppressed scar formation after spinal cord injury.

摘要

脊髓损伤后的瘢痕形成被视为轴突再生和功能恢复的障碍。埃坡霉素B可适度稳定微管,主要用于抗肿瘤治疗。它还能减少脊髓损伤后的瘢痕组织形成并促进轴突再生。本研究的目的是探讨微管稳定试剂埃坡霉素B通过作用于脊髓损伤后周细胞来减少纤维化瘢痕形成的作用及机制。建立大鼠脊髓损伤模型,于T10椎体水平进行背部完全横断。埃坡霉素B组大鼠在损伤后第1天和第15天腹腔注射埃坡霉素B(0.75mg/kg),对照组注射生理盐水。埃坡霉素B组神经元胶质抗原2、血小板衍生生长因子受体β和纤连蛋白蛋白表达显著低于对照组,但β-微管蛋白蛋白表达更高。损伤部位的胶质纤维酸性蛋白不受埃坡霉素B治疗的影响。埃坡霉素B组的巴索、贝蒂和布雷斯纳汉运动评分显著高于对照组。本研究结果表明,埃坡霉素B可减少脊髓损伤后周细胞数量,抑制细胞外基质形成,并抑制瘢痕形成。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/956f/5399728/cbcb6e1f4304/NRR-12-478-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/956f/5399728/073fed1623e6/NRR-12-478-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/956f/5399728/4f360d91ff1f/NRR-12-478-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/956f/5399728/5fd6e84cfcc4/NRR-12-478-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/956f/5399728/cbcb6e1f4304/NRR-12-478-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/956f/5399728/073fed1623e6/NRR-12-478-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/956f/5399728/4f360d91ff1f/NRR-12-478-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/956f/5399728/5fd6e84cfcc4/NRR-12-478-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/956f/5399728/cbcb6e1f4304/NRR-12-478-g006.jpg

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