中国组织工程研究 ›› 2024, Vol. 28 ›› Issue (11): 1772-1779.doi: 10.12307/2023.964

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

脊髓损伤后细胞焦亡调控机制及治疗策略

尚文雅1,任亚锋2,李  冰2,韦慧麟1,张芝兰1,黄晓萌1,黄  靖1   

  1. 1河南中医药大学,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
  • 收稿日期:2023-01-10 接受日期:2023-02-11 出版日期:2024-04-18 发布日期:2023-07-27
  • 通讯作者: 任亚锋,主任医师,硕士生导师,河南中医药大学第一附属医院,河南省郑州市 450000
  • 作者简介:尚文雅,女,2000 年生,河南省许昌市人,汉族,河南中医药大学在读硕士。
  • 基金资助:
    河南省中医管理局国家中医临床研究基地科研专项课题(2018JDZX010),项目负责人:任亚锋;河南省中医药科学研究专项课题(20-21ZY2164),项目参与人:任亚锋;河南省中医药科学研究专项课题(2021JDZY022),项目负责人:任亚锋

Regulatory mechanisms and therapeutic strategies for pyroptosis after spinal cord injury

Shang Wenya1, Ren Yafeng2, Li Bing2, Wei Huilin1, Zhang Zhilan1, Huang Xiaomeng1, Huang Jing1   

  1. 1Henan University of Chinese Medicine, Zhengzhou 450046, Henan Province, China; 2The First Affiliated Hospital of Henan University of Chinese Medicine, Zhengzhou 450000, Henan Province, China
  • Received:2023-01-10 Accepted:2023-02-11 Online:2024-04-18 Published:2023-07-27
  • Contact: Ren Yafeng, Chief physician, Master’s supervisor, the First Affiliated Hospital of Henan University of Chinese Medicine, Zhengzhou 450000, Henan Province, China
  • About author:Shang Wenya, Henan University of Chinese Medicine, Zhengzhou 450046, Henan Province, China
  • Supported by:
    National TCM Clinical Research Base Scientific Research Special Project of Henan Provincial TCM Administration, No. 2018JDZX010 (to RYF); Special Project of Henan Provincial TCM Scientific Research, No. 20-21ZY2164 (to RYF [project participant]); Special Project of Henan Provincial TCM Scientific Research, No. 2021JDZY022 (to RYF)

摘要:


文题释义:

细胞焦亡:是一种以促炎活性为特征的程序性细胞死亡,由半胱氨酸蛋白酶(Caspase-1/4/5/11)激活,并由Gasdermin家族介导,导致细胞裂解死亡,释放炎性细胞内容物,加剧炎症反应,与脊髓损伤后继发性损伤阶段的发展密切相关。
脊髓损伤:可引起严重的运动和感觉障碍,显著降低患者的生活质量和预期寿命,减轻继发性神经元死亡和改善存活神经元功能被认为是脊髓损伤治疗的关键策略。由于其发病机制复杂,目前尚无有效的治疗脊髓损伤药物。


背景:调节细胞死亡和神经炎症是治疗脊髓损伤的两个重要途径,细胞焦亡是一种与神经炎症密切相关的程序性死亡模式,针对性靶向抑制脊髓损伤后焦亡,是一项有前景的治疗策略。

目的:归纳细胞焦亡在脊髓损伤中的分子机制、正负向调节因子及治疗策略的研究进展。
方法:以“spinal cord injury,pyroptosis,nucleotide-binding oligomerization domain-like receptor protein 3(NLRP3),Caspase,Gasdermin D(GSDMD),IL-1β,IL-18”为检索词,在PubMed和Web of Science数据库进行检索,最终纳入93篇英文文献。

结果与结论:①作为新发现的程序性死亡方式,细胞焦亡已被证实在脊髓损伤后继发性损伤阶段起重要作用。②在脊髓损伤后细胞焦亡的调节因子中,CD73、NRF2、GDF-11、多巴胺、FANCC和miR-423-5P可抑制细胞焦亡,TLR4和Aopps可促进细胞焦亡。③在治疗策略方面,中药活性成分丹皮酚、雷公藤红素、桦木酸、胡椒碱、山奈酚、喜树碱,各种细胞来源的外泌体,药物二甲双胍、拓扑替康、锂、锌和一氧化碳释放分子3能有效抑制焦亡,减轻脊髓继发性损伤,但这些药物的毒副反应和具体剂量有待深入研究。④细胞焦亡加重脊髓损伤的具体分子机制仍知之甚少,非经典途径及其他炎性小体的作用值得进一步探索。⑤目前脊髓损伤后焦亡的研究仅停留在动物实验阶段,尚无相关临床研究,且无批准的靶向治疗药物。⑥细胞焦亡在脊髓损伤后的应用具有巨大潜能,未来需继续研究其具体调控机制,为脊髓损伤的治疗提供新的作用靶点。

https://orcid.org/0000-0001-9626-8017(尚文雅)

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, 细胞焦亡, NLRP3, 半胱氨酸蛋白酶, Gasdermin D, 调节因子, 抗焦亡疗法

Abstract: BACKGROUND: Cell death and neuroinflammation are two important targets in the treatment of spinal cord injury. Pyroptosis is a programmed cell death closely related to neuroinflammation and targeted inhibition of pyroptosis after spinal cord injury is a promising therapeutic strategy.
OBJECTIVE: To summarize the molecular mechanism, positive and negative regulatory factors and therapeutic strategies of pyroptosis in spinal cord injury.
METHODS: The search terms were “spinal cord injury, pyroptosis, nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3), Caspase, Gasdermin D (GSDMD), IL-1β, IL-18” and 93 English literatures included in PubMed and Web of Science were finally selected for review. 
RESULTS AND CONCLUSION: As a newly discovered programmed cell death, pyroptosis has been shown to play an important role in the secondary injury stage after spinal cord injury. Among the regulatory factors of pyroptosis after spinal cord injury, CD73, NRF2, GDF-11, dopamine, FANCC and miR-423-5P could inhibit pyroptosis, while TLR4 and Aopps could promote pyroptosis. In terms of treatment, the active ingredients of traditional Chinese medicine (paeonol, tripterine, betulinic acid, piperine, kaempferol, and camptothecin), exosomes of various cell origins, and some drugs (metformin, topotecan, lithium, zinc, and carbon monoxide-releasing molecule 3) can effectively inhibit pyroptosis and reduce secondary spinal cord injury, but the toxicity and specific dose of these drugs need to be further studied. The specific molecular mechanism by which pyroptosis aggravates spinal cord injury is still poorly understood. The role of non-classical pathways and other inflammasomes is worth further exploration. At present, the research on pyroptosis after spinal cord injury only stays at the animal experiment stage. There are no related clinical studies and no approved targeted therapeutic drugs. (6) The application of pyroptosis after spinal cord injury has great potential, and its specific regulatory mechanism should be further studied in the future to provide a new target for the treatment of spinal cord injury. 

Key words: ">spinal cord injury, pyroptosis, NLRP3, Caspase, Gasdermin D, regulator, anti-pyroptosis therapy

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