中国组织工程研究 ›› 2023, Vol. 27 ›› Issue (5): 758-764.doi: 10.12307/2023.114

• 组织构建综述 tissue construction review • 上一篇    下一篇

非编码RNAs作为潜在治疗靶点在脊髓损伤中的调控效应

李志超1,谭国庆2,苏  辉1,徐展望2,薛海鹏1,2   

  1. 1山东中医药大学,山东省济南市  250014;2山东中医药大学附属医院,山东省济南市  250014
  • 收稿日期:2022-03-25 接受日期:2022-05-16 出版日期:2023-02-18 发布日期:2022-07-23
  • 通讯作者: 薛海鹏,博士,副主任医师,山东中医药大学,山东省济南市 250014;山东中医药大学附属医院,山东省济南市 250014
  • 作者简介:李志超,男,1995年生,山东省淄博市人,汉族,山东中医药大学在读博士研究生,主要从事骨质疏松、脊柱退行性疾病相关研究。
  • 基金资助:
    国家自然科学基金面上项目(82174410),项目负责人:徐展望;山东省自然科学基金重点项目(ZR202011050051),项目负责人:徐展望;济南市临床医学科技创新计划(202019148),项目负责人:薛海鹏

Regulatory role of non-coding RNAs as potential therapeutic targets in spinal cord injury

Li Zhichao1, Tan Guoqing2, Su Hui1, Xu Zhanwang2, Xue Haipeng1, 2   

  1. 1Shandong University of Traditional Chinese Medicine, Jinan 250014, Shandong Province, China; 2Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan 250014, Shandong Province, China
  • Received:2022-03-25 Accepted:2022-05-16 Online:2023-02-18 Published:2022-07-23
  • Contact: Xue Haipeng, MD, Associate chief physician, Shandong University of Traditional Chinese Medicine, Jinan 250014, Shandong Province, China; Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan 250014, Shandong Province, China
  • About author:Li Zhichao, MD candidate, Shandong University of Traditional Chinese Medicine, Jinan 250014, Shandong Province, China
  • Supported by:
    the National Natural Science Foundation of China (General Program), No. 82174410 (to XZW); Key Project of Shandong Natural Science Foundation, No. ZR202011050051 (to XZW); Jinan Municipal Clinical Medicine Science and Technology Innovation Program, No. 202019148 (to XHP)

摘要:

文题释义:
脊髓损伤:由原发性损伤和继发性损伤2个阶段组成。机械力(例如车祸或跌倒造成的伤害)导致椎骨骨折以及脊髓受压、牵拉和/或横断,造成原发性损伤。原发性损伤后引发继发性损伤,其特征是信号级联反应产生的微环境导致脊髓进一步损伤并抑制神经再生。
非编码RNA:是指不具有蛋白质编码潜力的RNA分子,占所有哺乳动物基因组产生的RNA的98%-99%,主要包括微小RNA、长链非编码RNA和环状RNA等。它们与核酸或其他分子积极相互作用,几乎参与了正常发育和各种疾病(包括脊髓损伤)中的所有细胞过程。

背景:尽管目前针对脊髓损伤复杂生理病理机制开展了众多研究,但仍缺乏令人满意的治疗方法。研究表明,在脊髓损伤后与氧化应激、炎症、细胞自噬和凋亡等继发性损伤相关的非编码RNAs均有差异表达。因此,非编码RNAs具有作为脊髓损伤后治疗靶点的潜力。
目的:综述非编码RNAs在脊髓损伤后的差异表达、功能作用和调控机制,以期为脊髓损伤的临床治疗提供新思路。
方法:以“spinal cord injury”AND“non-coding RNA”OR“microRNA”OR“long non-coding RNA”OR“circRNA”AND“oxidative stress” OR“inflammation”OR“autophagy”OR“apoptosis”为关键词,检索PubMed、Web of Science数据库;以“脊髓损伤”和“非编码RNA”或“微小RNA”或“长链非编码RNA”或“环状RNA”和“氧化应激”或“炎症”或“自噬”或“凋亡”为关键词检索CNKI、万方数据库。依照纳入和排除标准进行筛选,最终对75篇文献进行综述。
结果与结论:脊髓损伤后,与氧化应激、炎症、自噬和细胞凋亡等继发性损伤相关的非编码RNAs出现显著差异表达,导致靶基因表达差异和细胞功能发生变化。通过调节非编码RNAs拮抗氧化应激,干预小胶质细胞活化、极化和炎症通路以减轻炎症反应,维持适度水平细胞自噬和保持自噬通量通畅,以及抑制细胞凋亡,可能成为促进脊髓损伤修复的突破点。

https://orcid.org/ 0000-0002-5314-2112(李志超)

中国组织工程研究杂志出版内容重点:组织构建;骨细胞;软骨细胞;细胞培养;成纤维细胞;血管内皮细胞;骨质疏松;组织工程

关键词: 脊髓损伤, 细胞凋亡, 炎症, 氧化应激, 自噬, 微小RNAs, 长链非编码RNAs, 环状RNAs

Abstract: BACKGROUND: Although many studies have been carried out on the complex physiological and pathological mechanisms of spinal cord injury, there is still a lack of satisfactory treatment methods. Studies have shown that non-coding RNAs associated with secondary injuries, such as oxidative stress, inflammation, autophagy and apoptosis, are differentially expressed after spinal cord injury. Therefore, non-coding RNAs have potential as therapeutic targets after spinal cord injury.
OBJECTIVE: Based on the latest research progress, to review the functional roles and regulatory mechanisms of non-coding RNAs in spinal cord injury, in order to provide new ideas for clinical treatment of spinal cord injury.
METHODS: Using “spinal cord injury” AND “non-coding RNA” OR “microRNA” OR “long non-coding RNA” OR “circRNA” AND “oxidative stress” OR “inflammation” OR “autophagy” OR “apoptosis” as English and Chinese keywords, PubMed, Web of Science, CNKI and WanFang databases were searched. According to inclusion and exclusion criteria, 75 articles were reviewed.
RESULTS AND CONCLUSION: After spinal cord injury, non-coding RNAs associated with secondary injury such as oxidative stress, inflammation, autophagy and apoptosis were significantly differentially expressed, resulting in differential expression of target genes and changes in cell functions. Regulating non-coding RNAs to antagonize oxidative stress, intervening microglia activation, polarization and inflammatory pathways to reduce inflammation, maintaining moderate levels of autophagy and keeping autophagy flux unobstructed, and inhibiting apoptosis may be the breakthrough points to promote the repair of spinal cord injury.

Key words: spinal cord injury, apoptosis, inflammation, oxidative stress, autophagy, microRNAs, long non-coding RNAs, circular RNAs

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