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已发表论文
P2Y12 受体阻断可减轻脂多糖诱导的急性肺损伤，其机制与抑制炎性小体介导的细胞焦亡信号传导有关
Authors Zhang LF, Lin XM , Zeng ZH, Xie RC, Yi LT , Ma JF
Received 14 May 2025
Accepted for publication 29 October 2025
Published 5 November 2025 Volume 2025:19 Pages 9825—9844
DOI https://doi.org/10.2147/DDDT.S540354
Checked for plagiarism Yes
Review by Single anonymous peer review
Peer reviewer comments 2
Editor who approved publication: Dr Solomon Tadesse Zeleke
Lian-Fang Zhang,1 Xiao-Ming Lin,1 Zi-Heng Zeng,2 Rong-Cheng Xie,1 Li-Tao Yi,2 Jie-Fei Ma1,3
1Department of Critical Care Medicine, Zhongshan Hospital (Xiamen), Fudan University, Xiamen, Fujian, 361015, People’s Republic of China; 2Department of Chemical and Pharmaceutical Engineering, College of Chemical Engineering, Huaqiao University, Xiamen, Fujian, 361021, People’s Republic of China; 3Department of Critical Care Medicine, Zhongshan Hospital, Fudan University, Shanghai, 200032, People’s Republic of China
Correspondence: Jie-Fei Ma, Department of Critical Care Medicine, Zhongshan Hospital (Xiamen), Fudan University, 668 Jinhu Road, Xiamen, Fujian, 361015, People’s Republic of China, Email ma.jiefei@zs-hospital.sh.cn Li-Tao Yi, Department of Chemical and Pharmaceutical Engineering, College of Chemical Engineering, Huaqiao University, 668 Jimei Avenue, Xiamen, Fujian, 361021, People’s Republic of China, Email litaoyi@hqu.edu.cn
Purpose: Acute lung injury (ALI) is characterized by excessive inflammation and cell death, with no specific pharmacological treatment. P2Y12 receptor (P2Y12R) is implicated in regulating inflammation, but their role in ALI remains unclear. This study investigates the effects of P2Y12R antagonists including Clopidogrel, Prasugrel, and Ticagrelor on LPS-induced ALI in mice, focusing on inflammation and pyroptosis.
Methods: Mice were pre-treated with P2Y12R antagonists before LPS administration. Lung injury was assessed via histology, wet/dry ratio, myeloperoxidase (MPO) activity, and inflammatory cytokine levels in bronchoalveolar lavage fluid (BALF). Gene and protein levels of IL-1β, IL-6, TNF-α, and inflammasome components (NLRP3, ASC, Caspase-1, GSDMD) were measured. Ultrastructural changes were analyzed by transmission electron microscopy (TEM).
Results: P2Y12R antagonists reduced histological injury, pulmonary edema, and inflammatory cytokines in BALF, with Ticagrelor showing the most prominent effects. Gene and protein levels of IL-1β, IL-6, and TNF-α were decreased. P2Y12R antagonists also inhibited inflammasome activation and pyroptosis. TEM analysis showed reduced organelle damage in treated groups.
Conclusion: P2Y12R antagonists, particularly Ticagrelor, attenuate lung injury and were associated with suppression of the NLRP3/caspase-1/GSDMD pyroptotic signaling axis.
Keywords: P2Y12 receptor, P2Y12R, acute lung injury, ALI, NLRP3, pyroptosis
1Department of Critical Care Medicine, Zhongshan Hospital (Xiamen), Fudan University, Xiamen, Fujian, 361015, People’s Republic of China; 2Department of Chemical and Pharmaceutical Engineering, College of Chemical Engineering, Huaqiao University, Xiamen, Fujian, 361021, People’s Republic of China; 3Department of Critical Care Medicine, Zhongshan Hospital, Fudan University, Shanghai, 200032, People’s Republic of China
Correspondence: Jie-Fei Ma, Department of Critical Care Medicine, Zhongshan Hospital (Xiamen), Fudan University, 668 Jinhu Road, Xiamen, Fujian, 361015, People’s Republic of China, Email ma.jiefei@zs-hospital.sh.cn Li-Tao Yi, Department of Chemical and Pharmaceutical Engineering, College of Chemical Engineering, Huaqiao University, 668 Jimei Avenue, Xiamen, Fujian, 361021, People’s Republic of China, Email litaoyi@hqu.edu.cn
Purpose: Acute lung injury (ALI) is characterized by excessive inflammation and cell death, with no specific pharmacological treatment. P2Y12 receptor (P2Y12R) is implicated in regulating inflammation, but their role in ALI remains unclear. This study investigates the effects of P2Y12R antagonists including Clopidogrel, Prasugrel, and Ticagrelor on LPS-induced ALI in mice, focusing on inflammation and pyroptosis.
Methods: Mice were pre-treated with P2Y12R antagonists before LPS administration. Lung injury was assessed via histology, wet/dry ratio, myeloperoxidase (MPO) activity, and inflammatory cytokine levels in bronchoalveolar lavage fluid (BALF). Gene and protein levels of IL-1β, IL-6, TNF-α, and inflammasome components (NLRP3, ASC, Caspase-1, GSDMD) were measured. Ultrastructural changes were analyzed by transmission electron microscopy (TEM).
Results: P2Y12R antagonists reduced histological injury, pulmonary edema, and inflammatory cytokines in BALF, with Ticagrelor showing the most prominent effects. Gene and protein levels of IL-1β, IL-6, and TNF-α were decreased. P2Y12R antagonists also inhibited inflammasome activation and pyroptosis. TEM analysis showed reduced organelle damage in treated groups.
Conclusion: P2Y12R antagonists, particularly Ticagrelor, attenuate lung injury and were associated with suppression of the NLRP3/caspase-1/GSDMD pyroptotic signaling axis.
Keywords: P2Y12 receptor, P2Y12R, acute lung injury, ALI, NLRP3, pyroptosis