内质网应激在肝脏疾病中的研究进展

doi:10.12114/j.issn.1007-9572.2023.0545

摘要/Abstract

摘要： 大量研究证实内质网应激（ERS）与肝脏疾病的发生、发展密切相关，但ERS与肝脏疾病进展的关联机制目前尚未明确，还需进一步探索。诸多研究发现，适度的ERS能激活未折叠蛋白反应（UPR）以保护细胞，而严重或持续的ERS将诱导细胞凋亡。因此，探讨ERS在肝脏疾病发病机制中的作用可能有助于发现新的治疗策略。故本文就ERS和UPR在多种肝脏疾病中的研究现状及其潜在治疗策略进行阐述。

关键词: 肝病, 内质网应激, 未折叠蛋白反应, 细胞凋亡, 炎症

Abstract:

A large number of studies have confirmed that endoplasmic reticulum stress (ERS) is closely related to the development and progression of liver diseases, but the mechanism of the association between ERS and liver disease progression has not been clarified and needs to be further explored. Numerous studies have found that moderate ERS can activate the unfolded protein response (UPR) to protect cells, while severe or persistent ERS can induce apoptosis. Therefore, exploring the role of ERS in the pathogenesis of liver diseases may help to discover new therapeutic strategies. This paper describes the current research status and potential therapeutic strategies of ERS and UPR in various liver diseases.

Key words: Liver disease, Endoplasmic reticulum stress, Unfolded protein reaction, Cell apoptosis, Inflammation

中图分类号:

R 256.4

李川,吴云冲,杨颜颜,等. 内质网应激在肝脏疾病中的研究进展[J]. 中国全科医学, 2024, 27(21): 2679-2684. DOI: 10.12114/j.issn.1007-9572.2023.0545.
LI Chuan,WU Yunchong,YANG Yanyan, et al. Advances in Endoplasmic Reticulum Stress in Liver Diseases[J]. Chinese General Practice, 2024, 27(21): 2679-2684. DOI: 10.12114/j.issn.1007-9572.2023.0545.

图/表 1

图1 适应性未折叠蛋白反应和非适应性未折叠蛋白反应示意图注：ER=内质网，ERS=内质网应激，GRP78=葡萄糖调节蛋白78，PERK=蛋白激酶R样内质网激酶，IRE1α=肌醇需求蛋白1，ATF6=活化转录因子6，EIF2α=异源三聚体真核生物翻译起始因子2α，ATF4=活化转录因子4，XBP1s=剪接X盒结合蛋白1，ATF6α=活化转录因子α，ATF6β=活化转录因子6β，CHOP=C/EBP同源蛋白，ASK1=凋亡信号调节蛋白1，BCL2=凋亡信号相关蛋白，ERAD=ER相关降解，JNK1=Jun N末端蛋白1，TRAF2=肿瘤坏死因子受体相关因子2，CAMKⅡ=钙调蛋白依赖蛋白激酶Ⅱ，IP3R1=1，4，5-三磷酸肌醇受体1，Nucleus=细胞核，Autophay=自噬，Apotosis=凋亡。

Figure 1 Schematic diagram of adaptive unfolded protein response and maladaptive unfolded protein response

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