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

Q3 Medicine
生理学报 Pub Date : 2024-08-25
Lu Shi, Man Huang, Si-An Chen, Jun-Peng Xu, Qi-Hao Zhang, Wen-Jie Cao, Yun-Na Tian, Xiao-Ting Wang, Wan-Tie Wang
{"title":"[2-DG improves lung ischemia/reperfusion injury by inhibiting NLRP3-mediated pyroptosis in rats].","authors":"Lu Shi, Man Huang, Si-An Chen, Jun-Peng Xu, Qi-Hao Zhang, Wen-Jie Cao, Yun-Na Tian, Xiao-Ting Wang, Wan-Tie Wang","doi":"","DOIUrl":null,"url":null,"abstract":"<p><p>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.</p>","PeriodicalId":7134,"journal":{"name":"生理学报","volume":null,"pages":null},"PeriodicalIF":0.0000,"publicationDate":"2024-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"生理学报","FirstCategoryId":"1087","ListUrlMain":"","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"Medicine","Score":null,"Total":0}
引用次数: 0

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.

[2-DG 通过抑制 NLRP3 介导的大鼠热蛋白沉积,改善肺缺血/再灌注损伤]。
本研究旨在探讨2-脱氧葡萄糖(2-DG)对肺缺血再灌注(I/R)损伤的保护作用是否是通过抑制核苷酸结合寡聚化结构域样受体蛋白3(NLRP3)介导的大鼠热蛋白沉积来实现的。雄性 Sprague-Dawley 大鼠被随机分为对照组、2-DG 组、肺 I/R 损伤组(I/R 组)和 2-DG+I/R 组。肺缺血前 1 小时腹腔注射 2-DG(0.7 克/千克)。光镜下测量组织结构。检测肺损伤参数。丙二醛(MDA)、髓过氧化物酶(MPO)和乳酸的含量由市售试剂盒测定。用 ELISA 检测 IL-1β 和 IL-18 的水平。采用 Western 印迹、qRT-PCR 和免疫荧光染色法检测糖酵解和热解相关指标的表达变化。结果表明,对照组与 2-DG 组的各项指标无明显差异。但I/R组的肺损伤指标、氧化应激反应、乳酸含量、IL-1β和IL-18水平均显著升高。与对照组相比,I/R组糖酵解和热渗透相关指标,包括己糖激酶2(HK2)、丙酮酸激酶2(PKM2)、NLRP3、Gasdermin超家族成员GSDMD-N、裂解-Caspase1、裂解-IL-1β和裂解-IL-18的蛋白表达水平以及HK2、PKM2和NLRP3的基因表达水平均明显上调。免疫荧光染色也检测到 HK2 和 NLRP3 的表达增加。与 I/R 组相比,2-DG+I/R 组的肺泡结构和炎症浸润明显改善,肺损伤参数降低,糖酵解和热解相关指标的表达减少。这些结果表明,2-DG 可能通过抑制 NLRP3 介导的大鼠热蛋白沉积来防止肺 I/R 损伤。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
求助全文
约1分钟内获得全文 求助全文
来源期刊
生理学报
生理学报 Medicine-Medicine (all)
CiteScore
1.20
自引率
0.00%
发文量
4820
期刊介绍: Acta Physiologica Sinica (APS) is sponsored by the Chinese Association for Physiological Sciences and Shanghai Institutes of Biological Sciences, Chinese Academy of Sciences (CAS), and is published bimonthly by the Science Press, China. APS publishes original research articles in the field of physiology as well as research contributions from other biomedical disciplines and proceedings of conferences and symposia of physiological sciences. Besides “Original Research Articles”, the journal also provides columns as “Brief Review”, “Rapid Communication”, “Experimental Technique”, and “Letter to the Editor”. Articles are published in either Chinese or English according to authors’ submission.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信