河北医学2024，Vol.30Issue(8)：1279-1284,6.DOI:10.3969/j.issn.1006-6233.2024.08.09
橘皮素调节TXNIP/NLRP3信号通路对重症肺炎大鼠细胞焦亡的影响
Impact of Tangeretin on TXNIP/NLRP3 Signaling Pathway Regulation and Cell Pyroptosis in Severe Pneumonia Rats
摘要
Abstract
Objective:This study aimed to explore the influence of tangeretin on the TXNIP/NLRP3 sig-naling pathway in regulating cell pyroptosis in severe pneumonia rats.Methods:Sprague-Dawley rats were di-vided into control group,severe pneumonia group,low-dose tangeretin group,high-dose tangeretin group,high-dose tangeretin+pcDNA group,and high-dose tangeretin+pcDNA-TXNIP(TXNIP activator)group,with 12 rats in each group.Except for the control group,all other groups were induced to establish a severe pneumonia rat model by tracheal instillation of Klebsiella pneumoniae.Drug administration began immediately after successful modeling and continued for 4 weeks.Lung function parameters including peak expiratory flow(PEF)and forced vital capacity(FVC)were monitored using an animal lung function meter.Levels of inter-leukin(IL)-1β and IL-18 in bronchoalveolar lavage fluid were measured by ELISA.Changes in lung wet-to-dry weight ratio were evaluated.Lung histopathological changes were assessed by HE staining.Cell pyropto-sis in lung tissues was detected using propidium iodide(PI)staining.Expression levels of TXNIP,NLRP3,cleaved caspase-1,and N-terminal fragment of gasdermin D(GSDMD-N)in lung tissues were analyzed by Western blot.Results:Compared with the control group,rats in the severe pneumonia group showed severe lung tissue damage,decreased PEF and FVC,increased levels of IL-1β and IL-18 in bronchoalveolar lavage fluid,increased lung wet-to-dry weight ratio,elevated cell pyroptosis rate in lung tissues,and increased ex-pression of TXNIP,NLRP3,cleaved caspase-1,and GSDMD-N proteins(P＜0.05).Compared with the se-vere pneumonia group,rats in the low-dose tangeretin and high-dose tangeretin groups exhibited improved lung tissue damage,increased PEF and FVC,decreased levels of IL-1β and IL-18 in bronchoalveolar lavage fluid,decreased lung wet-to-dry weight ratio,reduced cell pyroptosis rate in lung tissues,and decreased ex-pression of TXNIP,NLRP3,cleaved caspase-1,and GSDMD-N proteins(P＜0.05).The protective effect of high-dose tangeretin on severe pneumonia was reversed by pcDNA-TXNIP.Conclusion:Tangeretin may inhibit inflammation and cell pyroptosis in severe pneumonia rats by blocking the TXNIP/NLRP3 pathway.关键词
橘皮素/硫氧还蛋白互作蛋白/含NLR家族PYRIN域蛋白3信号通路/重症肺炎/炎症/焦亡Key words
Tangeretin/TXNIP/NLRP3 signaling pathway/Severe pneumonia/Inflammation/Pyroptosis引用本文复制引用
周红,张佩佩,刘会雪,郭楠..橘皮素调节TXNIP/NLRP3信号通路对重症肺炎大鼠细胞焦亡的影响[J].河北医学,2024,30(8):1279-1284,6.基金项目
河北中医药管理局科研计划项目,(编号:2015216) （编号:2015216）
