Tetramethylpyrazine ameliorates endotoxin-induced acute lung injury by relieving Golgi stress via the Nrf2/HO-1 signaling pathway

BMC Pulmonary Medicine

Research

Yang Ma¹  Jianbo Yu¹  Jia Shi¹  Shaona Li¹  Shuan Dong¹  Xiangyun Li¹  Simeng He²  Bing Zhang³  Yexiang Xu³  Yanting Wang³  Cuicui Liu³  Xiangkun Li³  Youzhuang Zhu³ 

[1]Department of Anesthesiology and Critical Care Medicine, Tianjin Nankai Hospital, Tianjin Medical University, 300100, Tianjin, China

[2]Department of Anesthesiology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, 250000, Jinan, Shandong Province, China

[3]Department of Anesthesiology, The Affiliated Hospital of Qingdao University, 266000, Qingdao, Shandong Province, China

关键词: Tetramethylpyrazine (TMP);    Endotoxin;    Acute lung injury;    Golgi stress;    Nuclear factor erythroid-2 related factor 2 (Nrf2);    Heme oxygenase-1 (HO-1);   

DOI  :  10.1186/s12890-023-02585-3

 received in 2023-03-15, accepted in 2023-07-26,  发布年份 2023

来源: Springer

【 摘 要 】

PurposeEndotoxin-induced acute lung injury (ALI) is a severe disease caused by an imbalanced host response to infection. It is necessary to explore novel mechanisms for the treatment of endotoxin-induced ALI. In endotoxin-induced ALI, tetramethylpyrazine (TMP) provides protection through anti-inflammatory, anti-apoptosis, and anti-pyroptosis effects. However, the mechanism of action of TMP in endotoxin-induced ALI remains unclear. Here, we aimed to determine whether TMP can protect the lungs by inhibiting Golgi stress via the Nrf2/HO-1 pathway.Methods and resultsUsing lipopolysaccharide (LPS)-stimulated C57BL/6J mice and MLE12 alveolar epithelial cells, we observed that TMP pretreatment attenuated endotoxin-induced ALI. LPS + TMP group showed lesser lung pathological damage and a lower rate of apoptotic lung cells than LPS group. Moreover, LPS + TMP group also showed decreased levels of inflammatory factors and oxidative stress damage than LPS group (P < 0.05). Additionally, LPS + TMP group presented reduced Golgi stress by increasing the Golgi matrix protein 130 (GM130), Golgi apparatus Ca2+/Mn2+ ATPases (ATP2C1), and Golgin97 expression while decreasing the Golgi phosphoprotein 3 (GOLPH3) expression than LPS group (P < 0.05). Furthermore, TMP pretreatment promoted Nrf2 and HO-1 expression (P < 0.05). Nrf2-knockout mice or Nrf2 siRNA-transfected MLE12 cells were pretreated with TMP to explore how the Nrf2/HO-1 pathway affected TMP-mediated Golgi stress in endotoxin-induced ALI models. We observed that Nrf2 gene silencing partially reversed the alleviating effect of Golgi stress and the pulmonary protective effect of TMP.ConclusionOur findings showed that TMP therapy reduced endotoxin-induced ALI by suppressing Golgi stress via the Nrf2/HO-1 signaling pathway in vivo and in vitro.

【 授权许可】

CC BY   
© BioMed Central Ltd., part of Springer Nature 2023

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