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

doi:10.3969/j.issn.1006-6233.2024.08.09

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Abstract Objective: This study aimed to explore the influence of tangeretin on the TXNIP/NLRP3 signaling pathway in regulating cell pyroptosis in severe pneumonia rats.Methods: Sprague-Dawley rats were divided 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 interleukin (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 pyroptosis 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 expression of TXNIP, NLRP3, cleaved caspase-1, and GSDMD-N proteins (P<0.05). Compared with the severe 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 expression 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.

Key words： Tangeretin TXNIP/NLRP3 signaling pathway Severe pneumonia Inflammation Pyroptosis

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	ZHOU Hong
	ZHANG Peipei
	LIU Huixue
	et al

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ZHOU Hong,ZHANG Peipei,LIU Huixue, et al. Impact of Tangeretin on TXNIP/NLRP3 Signaling Pathway Regulation and Cell Pyroptosis in Severe Pneumonia Rats[J]. HeBei Med, 2024, 30(8): 1279-1284.

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http://www.hbyxzzs.cn/EN/10.3969/j.issn.1006-6233.2024.08.09 OR http://www.hbyxzzs.cn/EN/Y2024/V30/I8/1279

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