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. 2025 Jul 15;52(1):710.
doi: 10.1007/s11033-025-10814-7.

The interaction between COX-2 and endoplasmic reticulum stress is involved in liver ischemia-reperfusion injury in mice

Chen Liang #  1 , Liping Guo #  1 , Xinyan Tian  1 , Zhidan Mu  1 , Mingyang Chen  1 , Yarong Hu  2 , Juan Su  3
Affiliations

The interaction between COX-2 and endoplasmic reticulum stress is involved in liver ischemia-reperfusion injury in mice

Chen Liang et al. Mol Biol Rep. .

Abstract

Objective: By establishing a mouse model of hepatic ischemia-reperfusion injury (HIRI), to investigate the effects of cyclooxygenase-2 (COX-2) and endoplasmic reticulum stress (ERS) on HIRI and their interaction in HIRI.

Methods: C57BL/6J male mice were divided into four groups: Sham operation group (Sham group), hepatic ischemia-reperfusion (HIR) group, hepatic ischemia-reperfusion + Salubrinal (ER stress inhibitor) pretreatment group (HIR + Sal group), hepatic ischemia-reperfusion + NS398 (inhibitor of COX-2) pretreatment group (HIR + NS398 group). The levels of Aspartate transaminase (AST) and Alanine transaminase (ALT) in serum, the activity of Super Oxide Dismutase (SOD) and the content of malondialdehyde (MDA) in liver tissue were detected. The mRNA and protein expression of Glucose-regulated protein 78 (GRP78), C/EBP homologous protein (CHOP), phosphorylated eukaryotic translation initiation factor 2α (p-eIF2α) and COX-2/PTGS (Prostaglandin-endoperoxide synthase) in liver tissue were detected. The morphological changes and apoptosis of liver tissue were observed.

Results: Compared with the Sham group, the serum ALT and AST levels of the HIR group were increased, the SOD activity in the liver tissue was decreased, the MDA content and the expression of COX-2, p-eIF2α, GRP78 and CHOP protein were increased, and the staining results showed that hepatic sinusoidal congestion, a large number of hepatocyte death, inflammatory cell infiltration and apoptotic cells were significantly increased. The levels of ALT and AST decreased after Sal or NS398 pretreatment. SOD activity was increased, MDA content, COX-2, GRP78, CHOP mRNA and protein were decreased in liver tissue, and staining showed that liver tissue injury was improved.

Conclusion: In mice with HIR, COX-2 interacts with ERS to cause liver injury by regulating oxidative stress and apoptosis.

Keywords: COX-2; Cell apoptosis; Endoplasmic reticulum stress; Hepatic ischemia–reperfusion injury; Oxidative stress.

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Conflict of interest statement

Declarations. Competing interests: The authors have no relevant financial interests to disclose. Ethical approval: All animal experiments were approved by the Animal Welfare Committee of Dali University in accordance with the Laboratory Animal Guidelines for Ethical Review of Animal Welfare (China, 2024-PZ-98).

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