Jiarun Gu1, Xufei Ran2, Jin Deng3, Anqiang Zhang4, Guoxuan Peng5, Juan Du6, Dalin Wen7, Baowei Jiang8, Fei Xia9. 1. Department of Emergency Surgery, The Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou 550001, China; School of Clinical Medicine, Guizhou Medical University, Guiyang, Guizhou 550001, China. Electronic address: dr_gujiarun@163.com. 2. Department of Emergency Surgery, The Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou 550001, China; School of Clinical Medicine, Guizhou Medical University, Guiyang, Guizhou 550001, China. Electronic address: 707550968@qq.com. 3. Department of Emergency Surgery, The Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou 550001, China. Electronic address: gydengjin@yeah.net. 4. State Key Laboratory of Trauma, Burns and Combined Injury, Army Medical University, Chongqing 400010, China. Electronic address: zhanganqiang@126.com. 5. Department of Emergency Surgery, The Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou 550001, China; School of Clinical Medicine, Guizhou Medical University, Guiyang, Guizhou 550001, China. Electronic address: 1319389583@qq.com. 6. State Key Laboratory of Trauma, Burns and Combined Injury, Army Medical University, Chongqing 400010, China. Electronic address: dujuan1982727@163.com. 7. State Key Laboratory of Trauma, Burns and Combined Injury, Army Medical University, Chongqing 400010, China. Electronic address: 13452607810@163.com. 8. Department of Emergency Surgery, The Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou 550001, China; School of Clinical Medicine, Guizhou Medical University, Guiyang, Guizhou 550001, China. Electronic address: 1759635114@qq.com. 9. Department of Emergency Surgery, The Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou 550001, China. Electronic address: dr_xiafei@gmc.edu.cn.
Abstract
BACKGROUND: Neutrophil extracellular traps (NETs) are involved in the development of sepsis-induced acute respiratory distress syndrome (ARDS). Glycyrrhizin (GL), the main active ingredient of the traditional Chinese medicine Glycyrrhiza glabra, has anti-inflammatory, anti-viral, and immunomodulatory effects. OBJECTIVE: The study aims to explore the efficacy and potential mechanism of GL on sepsis-induced ARDS in mice. MATERIALS AND METHODS: Mice were randomly divided into 3 groups: Control, CLP, and GL + CLP. Mice sepsis ARDS model was induced by cecal ligation and puncture (CLP) followed by intraperitoneal GL treatment. Then, the 7-day survival rate of mice was recorded. The lung function of mice was determined by whole-body plethysmography. Lung pathology and scores were observed by hematoxylin-eosin staining. The wet/dry ratio (W/D) of the lung was measured by weighing method. The protein concentration in bronchoalveolar lavage fluid (BALF) was measured by the BCA method. NETs formation in lung tissue was detected by immunofluorescence. Furthermore, HMGB1、TLR9、MyD88 and IL6 expression in lung tissue were detected by western blot and by quantitative real-time PCR, respectively. RESULTS: The results showed that GL improved the survival rate, attenuated lung tissue injury and reduced the expression of inflammatory factors in mice with CLP-induced sepsis. Meanwhile, we confirmed that GL could inhibit TLR9 / MyD88 activation from reducing NETs formation by decreasing HMGB1 expression. The formation of NETs is regulated by HMGB1 / TLR9 / MyD88. In addition, GL improved lung function in mice with sepsis-induced ARDS. Lung function suggested that GL increased alveolar ventilation, alleviated ventilator fatigue and reduced airway resistance in mice with ARDS induced by sepsis. CONCLUSIONS: GL ameliorated sepsis-induced ARDS and reduced the NETs formation in lung tissues, which may be associated with the inhibition of the HMGB1 / TLR9 pathway.
BACKGROUND: Neutrophil extracellular traps (NETs) are involved in the development of sepsis-induced acute respiratory distress syndrome (ARDS). Glycyrrhizin (GL), the main active ingredient of the traditional Chinese medicine Glycyrrhiza glabra, has anti-inflammatory, anti-viral, and immunomodulatory effects. OBJECTIVE: The study aims to explore the efficacy and potential mechanism of GL on sepsis-induced ARDS in mice. MATERIALS AND METHODS: Mice were randomly divided into 3 groups: Control, CLP, and GL + CLP. Mice sepsis ARDS model was induced by cecal ligation and puncture (CLP) followed by intraperitoneal GL treatment. Then, the 7-day survival rate of mice was recorded. The lung function of mice was determined by whole-body plethysmography. Lung pathology and scores were observed by hematoxylin-eosin staining. The wet/dry ratio (W/D) of the lung was measured by weighing method. The protein concentration in bronchoalveolar lavage fluid (BALF) was measured by the BCA method. NETs formation in lung tissue was detected by immunofluorescence. Furthermore, HMGB1、TLR9、MyD88 and IL6 expression in lung tissue were detected by western blot and by quantitative real-time PCR, respectively. RESULTS: The results showed that GL improved the survival rate, attenuated lung tissue injury and reduced the expression of inflammatory factors in mice with CLP-induced sepsis. Meanwhile, we confirmed that GL could inhibit TLR9 / MyD88 activation from reducing NETs formation by decreasing HMGB1 expression. The formation of NETs is regulated by HMGB1 / TLR9 / MyD88. In addition, GL improved lung function in mice with sepsis-induced ARDS. Lung function suggested that GL increased alveolar ventilation, alleviated ventilator fatigue and reduced airway resistance in mice with ARDS induced by sepsis. CONCLUSIONS: GL ameliorated sepsis-induced ARDS and reduced the NETs formation in lung tissues, which may be associated with the inhibition of the HMGB1 / TLR9 pathway.
Authors: Felix Buder; Simina-Ramona Selejan; Mathias Hohl; Michael Kindermann; Christian Herr; Philipp M Lepper; Robert Bals; Bernd Salzberger; Felix Mahfoud; Michael Böhm Journal: PLoS One Date: 2022-10-17 Impact factor: 3.752