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2-DG improves lung ischemia/reperfusion injury by inhibiting NLRP3-mediated pyroptosis in rats

SHI Lu¹, HUANG Man², CHEN Si-An², XU Jun-Peng², ZHANG Qi-Hao², CAO Wen-Jie², TIAN Yun-Na², WANG Xiao-Ting², WANG Wan-Tie^2,*

¹College of Physical Education and Health, Yibin University, Yibin 644000, China；²Institute of Ischemia/Reperfusion Injury, Wenzhou Medical University, Wenzhou 325035, China

Abstract

The aim of this study was to investigate whether the protective effect of 2-deoxyglucose (2-DG) on lung ischemia/reperfusion (I/R) injury is mediated by inhibiting nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3)-mediated pyroptosis in rats. Male Sprague-Dawley rats were randomly divided into control group, 2-DG group, lung I/R injury group (I/R group) and 2-DG+I/R group. 2-DG (0.7 g/kg) was intraperitoneally injected 1 h prior to lung ischemia. The tissue structure was measured under light microscope. Lung injury parameters were detected. The contents of malondialdehyde (MDA), myeloperoxidase (MPO) and lactate were determined by commercially available kits. ELISA was used to detect the levels of IL-1β and IL-18. Western blot, qRT-PCR and immunofluorescence staining were used to measure the expression changes of glycolysis and pyroptosis related indicators. The results showed that there was no significant difference in the parameters between the control group and the 2-DG group. However, the lung injury parameters, oxidative stress response, lactic acid content, IL-1β, and IL-18 levels were significantly increased in the I/R group. The protein expression levels of glycolysis and pyroptosis related indicators including hexokinase 2 (HK2), pyruvate kinase 2 (PKM2), NLRP3, Gasdermin superfamily member GSDMD-N, cleaved-Caspase1, cleaved-IL-1β and cleaved-IL-18, and the gene expression levels of HK2, PKM2 and NLRP3 were markedly up-regulated in the I/R group compared with those in the control group. The expression of HK2 and NLRP3 was also increased detected by immunofluorescence staining. Compared with the I/R group, the 2-DG+I/R group exhibited significantly improved alveolar structure and inflammatory infiltration, reduced lung injury parameters, and decreased expression of glycolysis and pyroptosis related indicators. These results suggest that 2-DG protects against lung I/R injury possibly by inhibiting NLRP3-mediated pyroptosis in rats.

Key words: 2-deoxyglucose; glycolysis; pyroptosis; lung ischemia/reperfusion injury

Received: 　　Accepted:

Corresponding author: 王万铁　　E-mail:

DOI: 10.13294/j.aps.2024.0050

Citing This Article：

SHI Lu, HUANG Man, CHEN Si-An, XU Jun-Peng, ZHANG Qi-Hao, CAO Wen-Jie, TIAN Yun-Na, WANG Xiao-Ting, WANG Wan-Tie. 2-DG improves lung ischemia/reperfusion injury by inhibiting NLRP3-mediated pyroptosis in rats. Acta Physiol Sin 2024; 76 (4): 517-525 (in Chinese with English abstract).