Research progress in the role of NLRP3 inflammasome in hepatic ischemia-reperfusion injury

doi:10.16352/j.issn.1001-6325.2026.07.1004

Abstract

Abstract: Hepatic ischemia-reperfusion injury (HI/RI) is an inevitable pathophysiological process in liver surgery and is an important factor leading to severe postoperative complications. Its mechanism is complex, involving multiple pathways such as oxidative stress, intracellular calcium overload, and inflammatory response. In recent years, as an important regulatory hub of the innate immune response, the NOD-like receptor thermal protein domain associated protein 3(NLRP3) inflammasome has played a core role in HI/RI. This article reviews the structure and function of the NLRP3 inflammasome, its activation mechanism in HI/RI to identify the core role of this molecule and to explore the research status and challenges of various intervention strategies targeting NLRP3, providing new theoretical perspectives and orientation for clinical prevention and treatment of HI/RI.

Key words: inflammasome, hepatic ischemia-reperfusion injury, pyroptosis, inflammatory response, targeted therapy

CLC Number:

R392

LIU Cuiling, YU Shuna. Research progress in the role of NLRP3 inflammasome in hepatic ischemia-reperfusion injury[J]. Basic & Clinical Medicine, 2026, 46(7): 1004-1008.

References

[1] Xia K, Wang T, Chen Z, et al. Hepatocellular SETDB1 regulates hepatic ischemia-reperfusion injury through targeting lysine methylation of ASK1 signal[J]. Research (Wash D C), 2023, 6: 0256.doi:10.34133/research.0256.
[2] Luo L, Wang F, Xu X, et al. STAT3 promotes NLRP3 inflammasome activation by mediating NLRP3 mitochon-drial translocation[J]. Exp Mol Med, 2024, 56: 1980-1990.
[3] Yan H, Luo B, Wu X, et al. Cisplatin induces pyroptosis via activation of MEG3/NLRP3/caspase-1/GSDMD pathway in triple-negative breast cancer[J]. Int J Biol Sci, 2021, 17: 2606-2621.
[4] Lin J, Li F, Jiao J, et al. Quercetin, a natural flavonoid, protects against hepatic ischemia-reperfusion injury via inhibiting Caspase-8/ASC dependent macrophage pyroptosis[J]. J Adv Res, 2025, 70: 555-569.
[5] Yao L, Cai H, Fang Q, et al. Piceatannol alleviates liver ischaemia/reperfusion injury by inhibiting TLR4/NF-κB/NLRP3 in hepatic macrophages[J]. Eur J Pharmacol, 2023, 960: 176149. doi: 10.1016/j.ejphar.2023.176149.
[6] Wang T, Fang Y, Zhang X, et al. Heme oxygenase-1 alleviates ischemia-reperfusion injury by inhibiting hepatocyte pyroptosis after liver transplantation in rats[J]. Front Biosci (Landmark Ed), 2023, 28: 275.doi:10.31083/j.fbl2810275.
[7] Chen X, Jiang C, Chen M, et al. SYK promotes the formation of neutrophil extracellular traps by inducing PKM2 nuclear translocation and promoting STAT3 phosphoryla-tion to exacerbate hepatic ischemia-reperfusion injury and tumor recurrence[J]. Mol Med, 2024, 30: 146. doi:10.1186/s10020-024-00907-7.
[8] Gu Y, Li Y, Zhang C, et al. BCL6 alleviates hepatic ischemia/reperfusion injury via recruiting SIRT1 to repress the NF-κB/NLRP3 pathway[J]. Transplantation, 2025, 109: e297-e310.
[9] Jiang C, Ding W, Hu Y, et al. Liver X receptor activation alleviates hepatic ischemia-reperfusion injury in diabetes by inhibiting NF-κB-NLRP3 activation[J]. Immun Inflamm Dis, 2025, 13: e70243. doi:10.1002/iid3.70243.
[10] Shehata H, El-Abhar HS, Abdallah DM, et al. From liver to kidney: telmisartan attenuates NLRP3 inflammasome-driven systemic inflammation and the iNOS/Hsp70 axis partially via the Mas receptor in a hepatic ischemia-reperfusion model[J]. Eur J Pharmacol, 2025, 1005: 178098.doi:10.1016/j.ejphar.2025.178098 .
[11] Yu W, Lyu J, Jia L, et al. Dexmedetomidine ameliorates hippocampus injury and cognitive dysfunction induced by hepatic ischemia/reperfusion by activating SIRT3-Mediated mitophagy and inhibiting activation of the NLRP3 inflammasome in young rats[J]. Oxid Med Cell Longev, 2021, 2021: 9797165.doi:10.1155/2020/7385458.
[12] Yang Y, Eguchi A, Mori C, et al. Dietary sulforaphane glucosinolate mitigates depression-like behaviors in mice with hepatic ischemia/reperfusion injury: A role of the gut-liver-brain axis[J]. J Psychiatr Res, 2024, 176: 129-139.
[13] Cruz-Sanabria F, Bruno S, Crippa A, et al. Optimizing the time and dose of melatonin as a sleep-promoting drug: a systematic review of randomized controlled trials and dose-response meta-analysis[J].J Pineal Res, 2024, 76: e12985.doi:10.1111/jpi.12985.
[14] El-Sisi AEE, Sokar SS, Shebl AM, et al. Octreotide and melatonin alleviate inflammasome-induced pyroptosis through inhibition of TLR4-NF-κB-NLRP3 pathway in hepatic ischemia/reperfusion injury[J].Toxicol Appl Pharmacol, 2021, 410: 115340.doi:10.1016/j.taap.2020.115340.
[15] Qin K, Liang W, Fragoulis A, et al. Sulforaphane regulates hepatic autophagy and apoptosis by modulating Kupffer cells' polarization via Nrf2/HO-1 pathway in the murine hemorrhagic shock/resuscitation model[J].Eur J Trauma Emerg Surg, 2025, 51: 218.doi:10.1007/s00068-025-02890-y.
[16] Zhang R, Fang Q, Yao L, et al. Taxifolin attenuates hepatic ischemia-reperfusion injury by enhancing PINK1/Parkin-mediated mitophagy[J].Eur J Pharmacol, 2024, 985: 177100.doi:10.1016/j.ejphar.2024.177100.
[17] Sun Q, Yang R, Chen T, et al. Icaritin attenuates ischemia-reperfusion injury by anti-inflammation, anti-oxidative stress, and anti-autophagy in mouse liver[J].Int Immunopharmacol, 2024, 138: 112533.doi:10.1016/j.intimp.2024.112533.
[18] Lu J, Hou W, Yang S, et al. Trans-anethole pretreatment ameliorates hepatic ischemia-reperfusion injury via regulation of soluble epoxide hydrolase[J].Int Immunophar-macol, 2023, 124: 110809.doi:10.1016/j.intimp.2023.110809.
[19] Eldafashi N, Waaz S,Taha FS Ali, et al. The protective role of two oxindole derivatives is mediated by modulating NLRP3/caspase-1 and PI3K/AKT pathways in a pre-clinical animal model of hepatic ischemia reperfusion injury[J].Life Sci, 2024, 352: 122872.doi:10.1016/j.lfs.2024.122872.