Hurtado-Navarro Laura, Angosto-Bazarra Diego, Pelegrín Pablo, Baroja-Mazo Alberto, Cuevas Santiago
Molecular Inflammation Group, Biomedical Research Institute of Murcia (IMIB), University Clinical Hospital Virgen de la Arrixaca, 30120 Murcia, Spain.
Department of Biochemistry and Molecular Biology B and Immunology, Faculty of Medicine, University of Murcia, 30100 Murcia, Spain.
Antioxidants (Basel). 2022 Apr 28;11(5):870. doi: 10.3390/antiox11050870.
Inflammasomes, particularly the nucleotide-binding oligomerization domain, leucine-rich repeat, and pyrin domain containing 3 (NLRP3) inflammasome, apparently serve as crucial regulators of the inflammatory response through the activation of Caspase-1 and induction of pro-inflammatory cytokines and pyroptotic cell death. Pyroptosis is a type of programmed cell death mediated by Caspase-1 cleavage of Gasdermin D and the insertion of its N-terminal fragment into the plasma membrane, where it forms pores, enabling the release of different pro-inflammatory mediators. Pyroptosis is considered not only a pro-inflammatory pathway involved in liver pathophysiology but also an important pro-fibrotic mediator. Diverse molecular mechanisms linking oxidative stress, inflammasome activation, pyroptosis, and the progression of liver pathologies have been documented. Numerous studies have indicated the protective effects of several antioxidants, with the ability to induce nuclear factor erythroid 2-related factor 2 (Nrf2) activity on liver inflammation and fibrosis. In this review, we have summarised recent studies addressing the role of the NLRP3 inflammasome and pyroptosis in the pathogenesis of various hepatic diseases, highlighting the potential application of Nrf2 inducers in the prevention of pyroptosis as liver protective compounds.
炎性小体，尤其是核苷酸结合寡聚化结构域、富含亮氨酸重复序列和含吡啉结构域的蛋白3（NLRP3）炎性小体，显然通过激活半胱天冬酶-1以及诱导促炎细胞因子和细胞焦亡，充当炎症反应的关键调节因子。细胞焦亡是一种程序性细胞死亡，由半胱天冬酶-1切割gasdermin D并将其N端片段插入质膜介导，在质膜上形成孔道，从而使不同的促炎介质得以释放。细胞焦亡不仅被认为是参与肝脏病理生理过程的促炎途径，也是一种重要的促纤维化介质。氧化应激、炎性小体激活、细胞焦亡与肝脏疾病进展之间的多种分子机制已有文献记载。大量研究表明，几种抗氧化剂具有保护作用，能够诱导核因子红细胞2相关因子2（Nrf2）活性，对肝脏炎症和纤维化产生影响。在本综述中，我们总结了近期关于NLRP3炎性小体和细胞焦亡在各种肝脏疾病发病机制中作用的研究，强调了Nrf2诱导剂作为肝脏保护化合物在预防细胞焦亡方面的潜在应用。
