摘要
背景:细胞焦亡是一种新发现的促炎性细胞程序性坏死。研究发现,细胞焦亡在椎间盘退变的发生与发展中起着重要作用。目的:综述有关细胞焦亡的分子机制及其在椎间盘退变中作用的最新研究进展,为椎间盘退变的机制研究提供新的思路,为椎间盘退变的治疗提供新的作用靶点。方法:应用计算机检索PubMed、万方数据和中国知网数据库,英文检索词为“Pyroptosis,Intervertebral disc degeneration,Nucleus pulposus,Caspase-1,NLRP3,Gasdermin D,IL-1β”,中文检索词为“细胞焦亡、椎间盘退变、髓核、半胱天冬酶1、核苷酸结合寡聚化结构域样受体蛋白3、Gasdermin D、白细胞介素1β”,经过筛选最终纳入66篇文章进行综述。结果与结论:①典型的细胞焦亡激活途径在椎间盘退变的进程中起重要作用,多种信号分子刺激椎间盘细胞引起NLRP3的活化,进而激活caspase-1,引起白细胞介素1β的产生,最终导致细胞焦亡和细胞外基质分解代谢增加,从而促进椎间盘退变。②细胞焦亡过程中的信号分子包括化学刺激(如脂多糖、活性氧、晚期糖基化终末产物、肿瘤坏死因子α及白细胞介素1β等)和机械刺激(如机械牵拉)。③细胞焦亡过程中涉及多种信号通路,最常见的是核转录因子κB信号通路和Wnt/β-catenin信号通路。④通过调节不同的作用靶点可抑制细胞焦亡的发生,主要靶向抑制剂包括核转录因子κB抑制剂Bay11-7082、SN50、NLRP3抑制剂MCC950、间充质干细胞来源的外泌体miRNA-410和褪黑素等。⑤细胞焦亡导致椎间盘退变的详细作用机制仍不清楚,细胞焦亡非典型激活途径和特殊激活途径在椎间盘退变中的作用还需要进一步的探索。⑥一些细胞焦亡靶向药物对椎间盘退变的治疗作用已经在细胞和动物模型中得到验证,但尚未应用于临床。⑦随着研究的深入,针对焦亡研制靶向药物可为椎间盘退变性疾病提供一种有前途的治疗策略。
BACKGROUND:Pyroptosis is a newly discovered type of pro-inflammatory programmed cell necrosis.It is found that cell pyroptosis plays an important role in the occurrence and development of intervertebral disc degeneration.OBJECTIVE:To review the research progress on the molecular mechanism of pyroptosis,the role of pyroptosis in intervertebral disc degeneration,provide new ideas for the study of the mechanism of intervertebral disc degeneration,and provide new targets for the treatment of intervertebral disc degeneration.METHODS:A computed-based online retrieval of PubMed,Wanfang,and CNKI databases were conducted with the keywords of“Pyroptosis,Intervertebral disc degeneration,Nucleus pulposus,Caspase-1,NLRP3,Gasdermin D,IL-1β”in English and Chinese,respectively.Finally,66 articles were selected to review.RESULTS AND CONCLUSION:(1)The typical activation pathway of cell pyroptosis plays an important role in the process of intervertebral disc degeneration.A variety of signal molecules stimulate intervertebral disc cells to activate NLRP3 and then activate caspase-1.Finally,it causes the production of IL-1β,which eventually leads to pyroptosis and increased extracellular matrix catabolism,so as to promote intervertebral disc degeneration.(2)Signal molecules in the process of pyrolysis include chemical stimulation(such as lipopolysaccharide,reactive oxygen species,advanced glycation end products,interleukin-1βand tumor necrosis factor-α)and mechanical stimulation(such as mechanical stretching).(3)A variety of signaling pathways are activated in the process of cell pyroptosis,such as nuclear factor-κB pathway and Wnt/β-catenin pathway.(4)The occurrence of pyroptosis can be inhibited by different action targets,such as nuclear factor-κB inhibitor Bay11-7082,SN50,NLRP3 inhibitor MCC950,exosomes derived from mesenchymal stem cells miRNA-410,and melatonin.(5)The detailed mechanism of cell pyroptosis leading to intervertebral disc degeneration is still unclear,and the role of atypical cell pyroptosis pathway in intervertebral disc degeneration still needs to be further explored.(6)The therapeutic effect of cytolytic targeted drugs on intervertebral disc degeneration has been verified in cell and animal models,but it has not been applied in clinic.(7)With the further research,targeted drugs for pyroptosis may become a promising treatment strategy for degenerative disc disease.
作者
张皓博
赵宇楠
杨学军
Zhang Haobo;Zhao Yunan;Yang Xuejun(Inner Mongolia Medical University,Hohhot 010050,Inner Mongolia Autonomous Region,China;Second Affiliated Hospital of Inner Mongolia Medical University,Hohhot 010050,Inner Mongolia Autonomous Region,China)
出处
《中国组织工程研究》
CAS
北大核心
2022年第9期1445-1451,共7页
Chinese Journal of Tissue Engineering Research
关键词
细胞焦亡
椎间盘退变
髓核
细胞外基质
激活
信号
白细胞介素1Β
pyroptosis
intervertebral disc degeneration
nucleus pulposus
extracellular matrix
activation
signal
interleukin-1β
作者简介
第一作者:张皓博,男,1996年生,内蒙古自治区鄂尔多斯市人,蒙古族,内蒙古医科大学在读硕士,医师,主要从事脊柱外科方向研究。https://orcid.org/0000-0001-6340-5492;通讯作者:杨学军,教授,主任医师,硕士生导师,内蒙古医科大学第二附属医院,内蒙古自治区呼和浩特市010050。https://orcid.org/0000-0002-6611-0494。
