Key Laboratory of Interventional Pulmonology of Zhejiang Province, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325015, China.
Department of Pulmonary and Critical Care Medicine, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, China.
Inflammation. 2024 Oct;47(5):1793-1805. doi: 10.1007/s10753-024-02009-2. Epub 2024 Apr 10.
Particulate matter (PM) induces and enhances oxidative stress and inflammation, leading to a variety of respiratory diseases, including acute lung injury. Exploring new treatments for PM-induced lung injury has long been of interest to researchers. Palmatine (PAL) is a natural extract derived from plants that has been reported in many studies to alleviate inflammatory diseases. Our study was designed to explore whether PAL can alleviate acute lung injury caused by PM. The acute lung injury model was established by instilling PM (4 mg/kg) into the airway of mice, and PAL (50 mg/kg and 100 m/kg) was administrated orally as the treatment groups. The effect and mechanism of PAL treatment were examined by immunofluorescence, immunohistochemistry, Western Blotting, ELISA, and other experiments. The results showed that oral administration of PAL (50 mg/kg and 100 m/kg) could significantly alleviate lung inflammation and acute lung injury caused by PM. In terms of mechanism, we found that PAL (50 mg/kg) exerts anti-inflammatory and anti-damage effects mainly by enhancing the activation of the Nrf2-related antioxidant pathway and inhibiting the activation of the NLRP3-related pyroptosis pathway in mice. These mechanisms have also been verified in our cell experiments. Further cell experiments showed that PAL may reduce intracellular reactive oxygen species (ROS) by activating Nrf2-related pathways, thereby inhibiting the activation of NLRP3-related pyroptosis pathway induced by PM in Beas-2B cell. Our study suggests that PAL can be a new option for PM-induced acute lung injury.
颗粒物（PM）诱导和增强氧化应激和炎症，导致多种呼吸道疾病，包括急性肺损伤。探索治疗 PM 诱导的肺损伤的新方法一直是研究人员关注的焦点。黄连碱（PAL）是一种从植物中提取的天然物质，在许多研究中被报道可缓解炎症性疾病。我们的研究旨在探索 PAL 是否可以缓解 PM 引起的急性肺损伤。通过向小鼠气道中注入 PM（4mg/kg）来建立急性肺损伤模型，并将 PAL（50mg/kg 和 100mg/kg）作为治疗组口服给药。通过免疫荧光、免疫组织化学、Western Blotting、ELISA 等实验来检查 PAL 治疗的效果和机制。结果表明，口服 PAL（50mg/kg 和 100mg/kg）可显著缓解 PM 引起的肺炎症和急性肺损伤。在机制方面，我们发现 PAL（50mg/kg）主要通过增强 Nrf2 相关抗氧化途径的激活和抑制 NLRP3 相关细胞焦亡途径的激活来发挥抗炎和抗损伤作用。这些机制在我们的细胞实验中也得到了验证。进一步的细胞实验表明，PAL 可能通过激活 Nrf2 相关途径来减少细胞内活性氧（ROS），从而抑制 PM 诱导的 Beas-2B 细胞中 NLRP3 相关细胞焦亡途径的激活。我们的研究表明，PAL 可以成为 PM 诱导的急性肺损伤的新选择。
