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Qinggan Huoxue Recipe regulates the cell pyroptosis mediated by Caspase-4/Caspase-3/GSDME to improve alcoholic liver injury
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DOI   10.11656/j.issn.1672-1519.2024.06.17
Key Words   Qinggan Huoxue Recipe;alcoholic liver disease;pyroptosis;Caspase-4/Caspase-3/GSDME pathway;traditional Chinese medicine compound
Author NameAffiliationE-mail
WU Yan Graduate School of Shanghai University of Traditional Chinese Medicine, Shanghai 200120, China
Central Hospital of Minhang District, Shanghai 201199, China 
 
SHENG Wei Institute of Digestive Disease, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China  
WANG Lishun Central Hospital of Minhang District, Shanghai 201199, China  
ZHANG Li Institute of Digestive Disease, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China  
JI Kang Central Hospital of Minhang District, Shanghai 201199, China  
CHEN Huijia Central Hospital of Minhang District, Shanghai 201199, China  
CHEN Junming Graduate School of Shanghai University of Traditional Chinese Medicine, Shanghai 200120, China
Central Hospital of Minhang District, Shanghai 201199, China 
chjm2008@126.com 
Abstract
    [Objective] To investigate the mechanism of Qinggan Huoxue Recipe(Qinggan Huoxue Recipe,QGHXR) in the prevention and treatment of alcoholic liver disease(ALD) by regulating Caspase-4/Caspase-3/GSDME pyroptosis pathway. [Methods] Eighteen C57BL/6 mice were randomly divided into control group,model group and QGHXR group to replicate the alcoholic liver disease model. Serum liver function and lipid levels were detected. Hematoxylin-eosin(HE) staining and oil red O staining were used to observe the pathological changes and lipid deposition in the liver. The expression of Caspase-4/Caspase-3/GSDME pathway related genes and proteins were detected by q-RT PCR,Western Blot and immunofluorescence staining. [Results] Compared with the control group,the liver TG level in model group was significantly increased(P<0.01),the serum ALT and AST levels were increased(P<0.05),and the serum IL-1β,IL-6 and TNF-α levels were increased(P<0.05). Liver tissue showed pathological changes and lipid deposition. The mRNA expression levels of IL-1β,IL-6,TNF-α and NLRP3 in liver tissue were increased. Compared with model group,the liver TG level in QGHXR group was significantly decreased(P<0.01),and the serum ALT,AST,TBIL and TBA levels were decreased(P<0.05). Serum TG,IL-6 and TNF-α levels were decreased(P<0.05) and serum HDL levels were increased(P<0.01). Serum lipid,liver pathological changes and lipid deposition were relieved. The levels of GsdmeN,Caspase-4,Caspase-3 and C-Caspase-3 genes and proteins were decreased(P<0.05). [Conclusion] QGHXR alleviates liver damage and lipid deposition in ALD mice by modulating the Caspase-4/Caspase-3/GSDME-mediated pyroptosis pathway.

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