中国神经再生研究(英文版)

中国神经再生研究(英文版) ›› 2023, Vol. 18 ›› Issue (2): 357-363.doi: 10.4103/1673-5374.346545

• 原著:视神经损伤修复保护与再生 • 上一篇    下一篇

缺血再灌注损伤视网膜神经元泛死亡样细胞死亡

  

  • 出版日期:2023-02-15 发布日期:2022-08-08
  • 基金资助:
    国家自然科学基金(81772134，81971891，82172196，81571939);中南大学研究生自主探索创新项目（2020zzts218）;湖南省研究生科研创新项目（CX20200116）;急救与创伤研究教育部重点实验室开放课题基金（KLET-202108）

PANoptosis-like cell death in ischemia/reperfusion injury of retinal neurons

Wei-Tao Yan1, #, Wen-Juan Zhao1, #, Xi-Min Hu2, Xiao-Xia Ban1, Wen-Ya Ning3, Hao Wan1, Qi Zhang1, *, Kun Xiong1, 4, 5 *   

  1. 1Department of Human Anatomy and Neurobiology, School of Basic Medical Science, Central South University, Changsha, Hunan Province, China; 2Department of Dermatology, Xiangya Hospital, Central South University, Changsha, Hunan Province, China; 3Department of Human Resources, Third Xiangya Hospital of Central South University, Changsha, Hunan Province, China; 4Hunan Key Laboratory of Ophthalmology, Changsha, Hunan Province, China; 5Key Laboratory of Emergency and Trauma, Ministry of Education, College of Emergency and Trauma, Hainan Medical University, Haikou, Hainan Province, China
  • Online:2023-02-15 Published:2022-08-08
  • Contact: Kun Xiong, MD, xiongkun2001@163.com; Qi Zhang, MD, zhangqi2014@csu.edu.cn.
  • Supported by:
    The study was supported by the National Natural Science Foundation of China, Nos. 81772134, 81971891, 82172196, 81571939 (all to KX); the Key Laboratory of Emergency and Trauma (Hainan Medical University) of Ministry of Education, No. KLET-202108 (to KX); the Fundamental Research Funds for the Central Universities of Central South University of China, No. 2020zzts218 (to WTY); Hunan Provincial Innovation Foundation for Postgraduate of China, No. CX20200116 (to WTY). 

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摘要：

泛死亡是一种新发现的调节性细胞死亡类型，包括焦亡、凋亡和程序性坏死三种表型，这些类型的细胞死亡在感染性和炎症性疾病的病理生理过程中同时发生。虽然作者既往基于文献证据挖掘的研究显示泛死亡可能发生在神经缺血再灌注损伤中，但关于泛死亡是否存在的实验研究仍几乎未见。研究采用体外和体内视网膜神经元缺血再灌注损伤模型，研究视网膜缺血再灌注损伤中是否存在类似泛死亡的细胞死亡（同时发生焦亡、凋亡和程序性坏死）。结果显示，在体外和体内，缺血再灌注损伤从形态学特征到基因水平都诱发了视网膜神经元的泛死亡样细胞死亡。而且缺血再灌注损伤条件下，泛死亡的重要成分（caspase-1，caspase-8和NLRP3）的表达也明显上调。这些结果表明，视网膜神经元缺血再灌注损伤中存在泛死亡样细胞死亡；该研究为今后研究视网膜神经元的泛死亡提供了初步实验线索。

https://orcid.org/0000-0002-3103-6028 (Kun Xiong); https://orcid.org/0000-0001-6300-6491 (Qi Zhang); https://orcid.org/0000-0002-2561-9673 (Wei-Tao Yan); https://orcid.org/0000-0002-3616-5347 (Wen-Juan Zhao)

Abstract: PANoptosis is a newly identified type of regulated cell death that consists of pyroptosis, apoptosis, and necroptosis, which simultaneously occur during the pathophysiological process of infectious and inflammatory diseases. Although our previous literature mining study suggested that PANoptosis might occur in neuronal ischemia/reperfusion injury, little experimental research has been reported on the existence of PANoptosis. In this study, we used in vivo and in vitro retinal neuronal models of ischemia/reperfusion injury to investigate whether PANoptosis-like cell death (simultaneous occurrence of pyroptosis, apoptosis, and necroptosis) exists in retinal neuronal ischemia/reperfusion injury. Our results showed that ischemia/reperfusion injury induced changes in morphological features and protein levels that indicate PANoptosis-like cell death in retinal neurons both in vitro and in vivo. Ischemia/reperfusion injury also significantly upregulated caspase-1, caspase-8, and NLRP3 expression, which are important components of the PANoptosome. These results indicate the existence of PANoptosis-like cell death in ischemia/reperfusion injury of retinal neurons and provide preliminary experimental evidence for future study of this new type of regulated cell death.

Key words: apoptosis, gasdermin-D (GSDMD), ischemia/reperfusion, mixed lineage kinase domain-like protein (MLKL), necroptosis, NOD-like receptor protein 3 (NLRP3), PANoptosis, pyroptosis, receptor-interacting protein kinase 3 (RIPK3), retinal neuron