摘要
背景:脊髓损伤是一种严重的中枢神经系统疾病,其特点是神经元再生能力弱,病理过程复杂。线粒体自噬是具有高度选择性的自噬,能够降解受损的线粒体,在能量供应、细胞代谢以及神经元存活等方面发挥重要作用。目的:探讨线粒体自噬的发生机制以及药物对线粒体自噬的影响,为脊髓损伤的治疗提供新的靶点。方法:在中国知网、万方数据库以“脊髓损伤,线粒体自噬,自噬,线粒体”为检索词,在PubMed数据库以“Spinal cord injury,Mitophagy,Autophagy,mitochondria”为检索词,检索线粒体自噬与脊髓损伤相关作用及机制的文章。结果与结论:①线粒体自噬水平的调节对脊髓损伤的治疗具有关键作用,其调控机制比较复杂,主要包括PINK1/Parkin、Nix/BNIP3L、FUNDC1、Atg蛋白等,除此之外,还发现GIT1调控途径、下调miRNA-124诱导途径等。②在治疗方面,雷帕霉素、乙酰左旋肉碱、红景天苷、桦木酸、麦芽酚等可以通过适当激活线粒体自噬抑制细胞凋亡,改善脊髓损伤;相反,罗格列酮则是通过抑制线粒体自噬改善脊髓损伤。这说明激活或抑制线粒体自噬都有可能会改善脊髓损伤,这与药物作用机制的不同有关,药物具体的作用机制还有待进一步研究。
BACKGROUND:Spinal cord injury is a serious disease of the central nervous system,characterized by weak regeneration of neurons and complex pathological processes.Mitochondrial autophagy is a highly selective autophagy that can degrade damaged mitochondria and plays an important role in energy supply,cell metabolism and neuronal survival.OBJECTIVE:To explore the mechanism of mitochondrial autophagy and the effects of drugs on mitochondrial autophagy,and provide a new target for the treatment of spinal cord injury.METHODS:In CNKI,Wanfang and PubMed databases,“spinal cord injury,mitophagy,autophagy,mitochondria”were used as search terms.We searched for articles on the role and mechanism of mitophagy and spinal cord injury.RESULTS AND CONCLUSION:(1)The regulation of mitochondrial autophagy level plays a key role in the treatment of spinal cord injury,and its regulatory mechanism is complex,mainly including PINK1/Parkin,Nix/BNIP3L,FUNDC1,and Atg proteins.In addition,GIT1 regulatory pathway and down-regulated miRNA-124 induction pathway were also found.(2)In terms of treatment,rapamycin,acetyl-L-carnitine,salidroside,betulinic acid,and maltol can inhibit apoptosis and improve spinal cord injury by appropriately activating mitochondrial autophagy.In contrast,rosiglitazone ameliorates spinal cord injury by inhibiting mitochondrial autophagy.This suggests that activation or inhibition of mitochondrial autophagy may improve spinal cord injury,which is related to the different mechanisms of drug action.The specific mechanism of action of the drugs remains to be further studied.
作者
丁轶群
李喜功
潘文明
张钦
Ding Yiqun;Li Xigong;Pan Wenming;Zhang Qin(Department of Spinal Surgery,Yuncheng Central Hospital Affiliated to Changzhi Medical College,Yuncheng 044000,Shanxi Province,China;Department of Spinal Surgery,First Affiliated Hospital,Zhejiang University School of Medicine,Hangzhou 310000,Zhejiang Province,China;Department of Spinal Surgery,Changshu No.2 People’s Hospital,Changshu 215500,Jiangsu Province,China)
出处
《中国组织工程研究》
CAS
北大核心
2023年第35期5727-5733,共7页
Chinese Journal of Tissue Engineering Research
基金
山西省自然科学基金(201901D111472),项目负责人:张钦。
关键词
脊髓损伤
中枢神经系统
线粒体自噬
线粒体
spinal cord injury
central nervous system
mitophagy
mitochondria
