Objective: To investigate the protective effect of
emodin in
acute pancreatitis (AP)-associated
lung injury and the underlying mechanisms. Methods:
NaT-AP model in rats was constructed using 3.5%
sodium taurocholate, and CER+LPS-AP model in mice was constructed using
caerulein combined with
Lipopolysaccharide. Animals were divided randomly into four groups:
sham, AP,
Ac-YVAD-CMK (
caspase-1 specific inhibitor, AYC), and
emodin groups. AP-associated
lung injury was assessed with H&E staining, inflammatory
cytokine levels, and
myeloperoxidase activity. Alveolar macrophages (AMs) pyroptosis was evaluated by flow cytometry. In bronchoalveolar lavage fluid, the levels of
lactate dehydrogenase and inflammatory
cytokines were measured by
enzyme-linked
immunosorbent assay. Pyroptosis-related
protein expressions were detected by Western Blot. Results:
Emodin, similar to the positive control AYC, significantly alleviated pancreas and lung damage in rats and mice. Additionally,
emodin mitigated the pyroptotic process of AMs by decreasing the level of inflammatory
cytokines and
lactate dehydrogenase. More importantly, the
protein expressions of NLRP3, ASC, Caspase1 p10, GSDMD, and GSDMD-NT in AMs were significantly downregulated after
emodin intervention. Conclusion:
Emodin has a
therapeutic effect on AP-associated
lung injury, which may result from the inhibition of NLRP3/Caspase1/GSDMD-mediated AMs pyroptosis signaling pathways.