脊髓损伤后细胞自噬的调控治疗机制及策略  

Regulatory mechanisms and therapeutic strategies for cellular autophagy after spinal cord injury

作　　者：杨溢珂 任亚锋[2] 李冰[2] 尚文雅 黄靖 郭佳 刘慧瑶 Yang Yike;Ren Yafeng;Li Bing;Shang Wenya;Huang Jing;Guo Jia;Liu Huiyao(Rehabilitation Medicine College,Henan University of Chinese Medicine,Zhengzhou 450046,Henan Province,China;The First Affiliated Hospital of Henan University of Chinese Medicine,Zhengzhou 450000,Henan Province,China)

机构地区：[1]河南中医药大学康复医学院,河南省郑州市450046 [2]河南中医药大学第一附属医院,河南省郑州市450000

出　　处：《中国组织工程研究》2025年第18期3885-3896,共12页Chinese Journal of Tissue Engineering Research

基　　金：河南省中医药科学研究专项(2022JDZX015,2021JDZY022),项目负责人:任亚锋;河南省“双一流”创建学科中医学科学研究专项(HSRP-DFCTCM-2023-1-25),项目负责人:任亚锋。

摘　　要：背景:细胞自噬通过自噬体-溶酶体降解途径来维持代谢和体内平衡,其与脊髓损伤后远端神经元细胞死亡和功能恢复受损密切相关,靶向细胞自噬来促进脊髓损伤后功能恢复是比较有前景的治疗方向。目的:对细胞自噬在脊髓损伤中的作用、细胞自噬的相关调控机制及治疗策略进行归纳总结。方法:以“spinal cord injury,autophagy,regulatory mechanisms,autophagy pathway,therapeutic target”为检索词,检索PubMed数据库;以“脊髓损伤,细胞自噬,调控机制,自噬通路,治疗靶点”为检索词,检索中国知网,最终纳入133篇英文文献和4篇中文文献。结果与结论:①细胞自噬作为细胞程序性死亡方式的一种,在脊髓损伤的进展和治疗中起着至关重要的作用。大多数研究表明,适度激活或促进自噬能够通过减少炎症反应和细胞凋亡来促进神经功能的恢复;少数研究表明,过度激活自噬相反,会阻碍脊髓损伤后的功能恢复。②脊髓损伤后,PI3K/AKT/mTOR、MAPK、AMPK、p53信号通路及Beclin-1、ATG和LC3等因子正向或负向调节细胞自噬的发生发展。③促进或抑制自噬可能是调控创伤性脊髓损伤发病机制的有前景的治疗策略,西药氨氯地平、二甲双胍、米诺环素,中医药山楂叶总黄酮、白桦脂酸、氧化苦参碱、针灸,以及细胞外囊泡、外泌体、活性氧响应的复合纤维等作为细胞自噬的激活剂,通过激活细胞自噬,减轻脊髓损伤的继发性损伤反应;而西药胰岛素样生长因子1、依拉达奉,中医药人参皂苷、针灸,以及水凝胶搭载碱性成纤维细胞生长因子作为细胞自噬的抑制剂,通过抑制过度的细胞自噬来促进脊髓损伤后的功能恢复。④细胞自噬的相关调控因子之间相互联系,而细胞自噬对于脊髓损伤的双向作用使得调控细胞自噬的主导因素尚需进一步探讨。⑤以自噬作为脊髓损伤治疗靶点的研究多在动物模型中进行,�BACKGROUND:Cellular autophagy maintains metabolism and in vivo homeostasis through the autophagosome-lysosome degradation pathway,which is closely related to the impaired cell death and functional recovery of distal neurons after spinal cord injury,and targeting cellular autophagy to promote the functional recovery of the spinal cord after spinal cord injury is a promising therapeutic direction.OBJECTIVE:To summarize the role of cellular autophagy in spinal cord injury,related regulatory mechanisms of cellular autophagy and therapeutic strategies.METHODS:PubMed and CNKI databases were searched with the search terms of“spinal cord injury,autophagy,regulatory mechanisms,autophagy pathway,therapeutic target”in English and Chinese,respectively.A total of 133 English and 4 Chinese articles were included for review.RESULTS AND CONCLUSION:(1)Autophagy,a form of programmed cell death,has been shown to play a crucial role in the progression and treatment of spinal cord injury.Most studies have shown that moderate activation or promotion of autophagy promotes neurological recovery by decreasing inflammatory responses and apoptosis.A few studies have reported that excessive activation of autophagy,on the contrary,impedes neurological recovery following spinal cord injury.(2)After spinal cord injury,PI3K/AKT/mTOR,MAPK,AMPK and p53 signaling pathways,and factors such as Beclin-1,ATG and LC3 regulate the initiation and development of cell autophagy in a positive or negative manner.(3)Promoting or inhibiting autophagy may be a promising therapeutic strategy to modulate the pathogenesis of traumatic spinal cord injury.And the drugs amlodipine,metformin,and minocycline,the Chinese medicines hawthorn leaf total flavonoids,betulinic acid,oxidized ginseng saponins,acupuncture,and extracellular vesicles of different cellular origins,exosomes and reactive oxygen speciesresponsive composite fibers as activators of cellular autophagy attenuate secondary injury in response to spinal cord injury by activating cellular autophagy,while

关 键 词：脊髓损伤 细胞自噬 调控机制 自噬通路 治疗靶点 自噬激活 自噬抑制 组织工程 工程化细胞 

分 类 号：R459.9[医药卫生—治疗学] R318[医药卫生—临床医学] R744