Tetrandrine alleviates silicosis by inhibiting canonical and non-canonical NLRP3 inflammasome activation in lung macrophages  

作　　者：Mei-yue Song Jia-xin Wang You-liang Sun Zhi-fa Han Yi-tian Zhou Ying Liu Tian-hui Fan Zhao-guo Li Xian-mei Qi Ya Luo Pei-ran Yang Bai-cun Li Xin-ri Zhang Jing Wang Chen Wang 

机构地区：[1]Beijing University of Chinese Medicine,Beijing,100029,China [2]Department of Pulmonary and Critical Care Medicine,Center of Respiratory Medicine,China-Japan Friendship Hospital,Beijing,100029,China [3]National Clinical Research Center for Respiratory Diseases,Beijing,100029,China [4]Tsinghua-Peking Center for Life Sciences,Department of Biology,College of Medicine,Tsinghua University,Beijing,100084,China [5]School of Pharmaceutical Sciences,Tsinghua University,Beijing,100084,China [6]Department of Basic Medical Sciences,School of Medicine,Tsinghua University,Beijing,100084,China [7]Institute of Basic Medical Sciences Chinese Academy of Medical Sciences,School of Basic Medicine Peking Union Medical College,Beijing,100730,China [8]Peking Union Medical College,Chinese Academy of Medical Sciences,Beijing,100730,China [9]Peking Union Medical College,MD Program,Beijing,100730,China [10]Department of Respiratory,The Second Affiliated Hospital of Harbin Medical University,Harbin,150086,China [11]Department of Pulmonary and Critical Care Medicine,The First Hospital of Shanxi Medical University,Taiyuan,030001,China

出　　处：《Acta Pharmacologica Sinica》2022年第5期1274-1284,共11页中国药理学报（英文版）

基　　金：This program was fund by Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences(CIFMS)(grant number:2018-I2M-1-001);the Non-profit Central Research Institute Fund of Chinese Academy of Medical Sciences(grant number:2019RC330001);National Natural Science Foundation of China(grant number:82090010).

摘　　要：Silicosis caused by inhalation of silica particles leads to more than ten thousand new occupational exposure-related deaths yearly.Exacerbating this issue,there are currently few drugs reported to effectively treat silicosis.Tetrandrine is the only drug approved for silicosis treatment in China,and despite more than decades of use,its efficacy and mechanisms of action remain largely unknown.Here,in this study,we established silicosis mouse models to investigate the effectiveness of tetrandrine of early and late therapeutic administration.To this end,we used multiple cardiopulmonary function test,as well as markers for inflammation and fibrosis.Moreover,using single cell RNA sequencing and transcriptomics of lung tissue and quantitative microarray analysis of serum from silicosis and control mice,our results provide a novel description of the target pathways for tetrandrine.Specifically,we found that tetrandrine attenuated silicosis by inhibiting both the canonical and non-canonical NLRP3 inflammasome pathways in lung macrophages.Taken together,our work showed that tetrandrine yielded promising results against silicosis-associated inflammation and fibrosis and further lied the groundwork for understanding its molecular targets.Our results also facilitated the wider adoption and development of tetrandirne,potentially accelerating a globally accepted therapeutic strategy for silicosis.

关 键 词：TETRANDRINE SILICOSIS MACROPHAGES NLRP3 inflammasome lung function 

分 类 号：R285.5[医药卫生—中药学]