聚乙二醇在神经功能重建领域应用及存在的问题

Application and existing problems of polyethylene glycol in the field of neurological reconstruction

背景:临床上广泛采用自体神经移植来达到神经修复的目的,但应用效果欠佳,而聚乙二醇的应用从细胞融合剂到水凝胶生物黏合剂再到促轴突融合神经修复新型材料等,因此若能联合聚乙二醇探索出加快神经功能重建的方法,可以更好地应用于临床,并且对神经再生与功能重建也具有重要意义。目的:阐述聚乙二醇在神经功能重建领域的应用进展。方法:利用PubMed和中国知网数据库,检索有关聚乙二醇促细胞融合以及聚乙二醇作用于神经修复的文献,检索时间为2020年10月至2021年3月,英文检索词为"PEG,polyethylene glycol,cell-fusion,nerve function reconstruction,nerve repair",中文检索词为"聚乙二醇、细胞融合、功能重建、神经修复"。根据纳入与排除标准对所有文章进行初筛后,保留相关性较高的61篇文章进行综述。结果与结论:(1)在一定条件下,70%聚乙二醇加入少量腺苷5’-三磷酸可加快损伤神经轴突快速生长,有效促进膜的融合,实现神经细胞结构和功能重建。(2)聚乙二醇自身浓度是促进体细胞融合的主要影响因素,当聚乙二醇浓度为35%,相对分子质量为4000,或者聚乙二醇浓度为50%,其相对分子质量为1000时,对细胞融合效率影响最大;其他次要影响因素包括融合细胞个数、反应温度和时间等。(3)进一步分析聚乙二醇促神经修复的机制发现,聚乙二醇可促进轴突融合,表现出恢复轴突形态的连续性和电生理功能的作用,但是否能在瓦勒氏变性之前实现轴突的有效连接还需进一步研究证明。(4)聚乙二醇应用前景较为广泛,未来可考虑将其应用在新型生物黏合剂的研发、神经修复支架改良、复合物水凝胶研制相关研究中,但关于聚乙二醇在神经功能重建领域的应用还有诸多问题未解决,如聚乙二醇诱导神经细胞融合对人体的长期影响、最大延迟治疗时间等问题,还需后续研究不断完善。

BACKGROUND:Autologous nerve transplantation is widely used clinically to achieve the purpose of nerve repair,but the application effect is not good.The application of polyethylene glycol ranges from cell fusion agents to hydrogel bioadhesives to new materials for promoting axon fusion nerve repair.Therefore,if it can be combined with polyethylene glycol to explore ways to speed up the reconstruction of nerve function,it can be better applied to the clinic,and it will also have important significance for nerve regeneration and functional reconstruction.OBJECTIVE:To describe the application and progress of polyethylene glycol in the field of neurological reconstruction.METHODS:PubMed and CNKI were used to retrieve articles about polyethylene glycol promoting cell fusion and polyethylene glycol acting on nerve repair.The search time was from October 2020 to March 2021.The English search terms were"PEG,polyethylene glycol,cell-fusion,nerve function reconstruction,nerve repair".The Chinese search terms were"polyethylene glycol,cell fusion,function reconstruction,nerve repair".All articles were initially screened according to the inclusion and exclusion criteria,and 61 articles with higher relevance were retained for review.RESULTS AND CONCLUSION:(1)Under certain conditions,70%polyethylene glycol was added with a small amount of adenosine 5’-triphosphate,which can accelerate the rapid growth of injured nerve axons,effectively promote membrane fusion,and realize the reconstruction of nerve cell structure and function.(2)The main factor affecting the efficiency of cell fusion is the concentration of polyethylene glycol itself.When its concentration is 35%,the relative molecular mass is 4000,or when the concentration is 50%,the relative molecular mass is 1000,greatest impact on cell fusion efficiency is found.The other minor influencing factors are the number of fused cells,the reaction temperature,and time.(3)In further research on different mechanisms of promoting nerve repair,polyethylene glycol can promote axon fusion,which is manifested in the restoration of the continuity of axon morphology and its electrophysiological function.However,further research is needed to prove whether the effective connection of axons can be realized before Wallerian degeneration.(4)Polyethylene glycol has a broad application prospect.In the future,it can be considered in the research and development of new bioadhesives,nerve repair stent improvement,and composite hydrogel research.However,the application of polyethylene glycol in the field of nerve function reconstruction still has many unresolved problems,such as the long-term effects of polyethylene glycol-induced neuronal fusion on the human body,and the maximum delay in treatment time,which need to be continuously improved by follow-up research.