Effect of exogenous spastin combined with polyethylene glycol on sciatic nerve injury

作     者：Yao-Fa Lin Zheng Xie Jun Zhou Hui-Hao Chen Wan-Wan Shao Hao-Dong Lin 

作者机构：Department of OrthopedicsChangzheng Hospitalthe Second Military Medical University Department of Orthopedicsthe Second People's Hospital of Karamay 

出 版 物：《Neural Regeneration Research》 (中国神经再生研究（英文版）)

年 卷 期：2019年第14卷第7期

页      面：1271-1279页

核心收录：

学科分类：0710[理学-生物学] 1002[医学-临床医学] 1001[医学-基础医学(可授医学、理学学位)] 10[医学] 

基　　金：supported by the National Natural Science Foundation of China,No.81772327(to HDL) the Shuguang Program of Shanghai Education Development Foundation and Shanghai Municipal Education Commission,China,No.15SG34(to HDL) 

主　　题：nerve regeneration peripheral nerves Wallerian degeneration polyethylene glycol axonal fusion spastin peripheral nerve injuries Masson staining microtubule neural regeneration 

摘      要：Polyethylene glycol can connect the distal and proximal ends of an injured nerve at the cellular level through axonal fusion to avoid Wallerian degeneration of the injured distal nerve and promote peripheral nerve regeneration.However,this method can only prevent Wallerian degeneration in 10% of axons because the cytoskeleton is not repaired in a timely fashion.Reconstruction of the cytoskeletal trunk and microtubule network has been suggested to be the key for improving the efficiency of axonal fusion.As a microtubule-severing protein,spastin has been used to enhance cytoskeletal reconstruction.Therefore,we hypothesized that spastin combined with polyethylene glycol can more effectively promote peripheral nerve regeneration.A total of 120 male Sprague-Dawley rats were randomly divided into sham,suture,polyethylene glycol,and polyethylene glycol + spastin groups.In suture group rats,only traditional nerve anastomosis of the end-to-end suture was performed after transection of the sciatic nerve.In polyethylene glycol and polyethylene glycol + spastin groups,50 μL of polyethylene glycol or 25 μL of polyethylene glycol + 25 μL of spastin,respectively,were injected immediately under the epineurium of the distal suture.Sensory fiber regeneration distance,which was used to assess early nerve regeneration at 1 week after surgery,was shortest in the suture group,followed by polyethylene glycol group and greatest in the polyethylene glycol + spastin group.Behavioral assessment of motor function recovery in rats showed that limb function was restored in polyethylene glycol and polyethylene glycol + spastin groups at 8 weeks after surgery.At 1,2,4 and 8 weeks after surgery,sciatic functional index values and percentages of gastrocnemius muscle wet weight were highest in the sham group,followed by polyethylene glycol + spastin and polyethylene glycol groups,and lowest in the suture group.Masson staining was utilized to assess the morphology of muscle tissue.Morphological changes in skeletal muscle were detectable in suture,polyethylene glycol,and polyethylene glycol + spastin groups at 1,2,4,and 8 weeks after surgery.Among them,muscular atrophy of the suture group was most serious,followed by polyethylene glycol and polyethylene glycol + spastin groups.Ultrastructure of distal sciatic nerve tissue,as detected by transmission electron microscopy,showed a pattern of initial destruction,subsequent disintegration,and gradual repair in suture,polyethylene glycol,and polyethylene glycol + spastin groups at 1,2,4,and8 weeks after surgery.As time proceeded,axonal ultrastructure gradually recovered.Indeed,the polyethylene glycol + spastin group was similar to the sham group at 8 weeks after surgery.Our findings indicate that the combination of polyethylene glycol and spastin can promote peripheral nerve regeneration.Moreover,the effect of this combination was better than that of polyethylene glycol alone,and both were superior to the traditional neurorrhaphy.This study was approved by the Animal Ethics Committee of the Second Military Medical University,China(approval No.CZ20170216) on March 16,2017.