Mechanism of Sanshi decoction in the treatment of gouty arthritis by NLRP3 inflammasome  

作　　者：PIAO Yong-zhu QI Ming-ming NIE Shuang-lian PAN Guo-xiong ZHANG Hao WANG Xin-bo 

机构地区：[1]First Affiliated Hospital,Heilongjiang University of Chinese Medicine,Harbin 150040,China [2]Heilongjiang University of Chinese Medicine,Harbin 150040,China

出　　处：《Journal of Hainan Medical University》2023年第23期26-33,共8页海南医学院学报（英文版）

基　　金：Heilongjiang Province Traditional Chinese Medicine Research Project(No.ZHY19-006)。

摘　　要：Objective:To observe the effect of Sanshi decoction on P2X7R/PKR pathway-mediated activation of macrophage NLRP3 inflammasome to elucidate the molecular mechanism of Sanshi decoction in the treatment of gouty arthritis.Methods:THP-1 macrophages were divided into control group,model group,low dose group,medium dose group,high dose group of Sanshi decoction and inhibitor group.The remaining groups were induced with monosodium urate crystals to establish a gouty arthritis cell model except the control group.Flow cytometry was used to detect macrophage ROS levels in each group,ELISA to detect MDA levels and SOD and GSH-PX activities in each group,and Western blot to detect P2X7R/PKR pathway and NLRP3 inflammasome-associated protein expression.We also used CCK-8 and flow cytometry to measure MH7A activity and apoptotic levels.Results:Compared with the control group,the ROS level,the content of MDA,the activities of SOD and GSH-PX were significantly increased,and the expression levels of NLRP3,full-length IL-1β,pro-IL-1β,full-length IL-18,pro-IL-18,full-length caspase-1,GSDMD-NT,P2X7R and p-PKR protein expression levels were significantly upregulated,and GSDMD-FL protein expression was significantly downregulated in the model group,and that the differences between them were statistically significant(P<0.05 and P<0.01).Compared with the model group,Sanshi decoction could reduce macrophage ROS levels,MDA content,SOD and GSHPX activities,and downregulate macrophage NLRP3,mature IL-1β,pro IL-1β,mature IL-18,pro IL-18,mature caspase-1,GSDMD-NT,P2X7R and p-PKR protein expression,and upregulate GSDMD-FL protein expression,with statistically significant differences(P<0.05 and P<0.01).In addition,MH7A activity was downregulated,and apoptosis level was upregulated in the model group in comparison with the control group,and differences were all significantly different(P<0.05).As compared to the model group,Sanshi decoction could significantly increase the activity of MH7A and inhibit the level of apoptosis,and that the differ

关 键 词：Gouty arthritis Sanshi decoction NLRP3 inflammasome P2X7R/PKR signaling pathway MACROPHAGES 

分 类 号：R259[医药卫生—中西医结合]