Zhejiang Provincial Key Laboratory of Interventional Pulmonology, Department of Pulmonary and Critical Care Medicine, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, China.
Zhejiang Provincial Key Laboratory of Interventional Pulmonology, Department of Pulmonary and Critical Care Medicine, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, China; Department of Pulmonary and Critical Care Medicine, The Quzhou Affiliated Hospital of Wenzhou Medical University, Quzhou People's Hospital, Quzhou, 324000, China.
Chem Biol Interact. 2024 May 25;395:111032. doi: 10.1016/j.cbi.2024.111032. Epub 2024 May 4.
Particulate matter (PM), the main component of air pollutants, emerges as a research hotspot, especially in the area of respiratory diseases. Paeoniflorin (PAE), known as anti-inflammatory and immunomodulatory effects, has been reported to alleviate acute lung injury (ALI). However, the effect of PAE on PM-induced ALI and the underlying mechanisms are still unclear yet. In this study, we established the PM-induced ALI model using C57BL/6J mice and BEAS-2B cells to explore the function of PAE. In vivo, mice were intraperitoneally injected with PAE (100 mg/kg) or saline 1 h before instilled with 4 mg/kg PM intratracheally and were euthanized on the third day. For lung tissues, HE staining and TUNEL staining were used to evaluate the degree of lung injury, ELISA assay was used to assess inflammatory mediators and oxidative stress level, Immunofluorescence staining and western blotting were applied to explore the role of pyroptosis and Nrf2 signaling pathway. In vitro, BEAS-2B cells were pretreated with 100 μM PAE before exposure to 200 μg/ml PM and were collected after 24h for the subsequent experiments. TUNEL staining, ROS staining, and western blotting were conducted to explore the underlying mechanisms of PAE on PM-induced ALI. According to the results, PAE can attenuate the degree of PM-induced ALI in mice and reduce PM-induced cytotoxicity in BEAS-2B cells. PAE can relieve PM-induced excessive oxidative stress and NLRP3 inflammasome-mediated pyroptosis. Additionally, PAE can also activate Nrf2 signaling pathway and inhibition of Nrf2 signaling pathway can impair the protective effect of PAE by aggravating oxidative stress and pyroptosis. Our findings demonstrate that PAE can attenuate PM-induced ALI by inhibiting oxidative stress and NLRP3 inflammasome-mediated pyroptosis, which is mediated by Nrf2 signaling pathway.
颗粒物（PM）是空气污染物的主要成分，成为研究热点，尤其是在呼吸系统疾病领域。芍药苷（PAE）具有抗炎和免疫调节作用，已被报道可减轻急性肺损伤（ALI）。然而，PAE 对 PM 诱导的 ALI 的影响及其潜在机制尚不清楚。在这项研究中，我们使用 C57BL/6J 小鼠和 BEAS-2B 细胞建立了 PM 诱导的 ALI 模型，以探讨 PAE 的作用。在体内，小鼠在气管内滴注 4mg/kg PM 前 1 小时腹腔内注射 PAE（100mg/kg）或生理盐水，并在第 3 天处死。对于肺组织，使用 HE 染色和 TUNEL 染色评估肺损伤程度，ELISA 测定评估炎症介质和氧化应激水平，免疫荧光染色和 Western blot 分析探索细胞焦亡和 Nrf2 信号通路的作用。在体外，BEAS-2B 细胞在暴露于 200μg/ml PM 前用 100μM PAE 预处理，24h 后收集用于后续实验。进行 TUNEL 染色、ROS 染色和 Western blot 分析以探讨 PAE 对 PM 诱导的 ALI 的潜在机制。结果表明，PAE 可减轻小鼠 PM 诱导的 ALI 程度，降低 BEAS-2B 细胞中 PM 诱导的细胞毒性。PAE 可减轻 PM 诱导的过度氧化应激和 NLRP3 炎性体介导的细胞焦亡。此外，PAE 还可以激活 Nrf2 信号通路，抑制 Nrf2 信号通路会通过加重氧化应激和细胞焦亡来损害 PAE 的保护作用。我们的研究结果表明，PAE 可通过抑制氧化应激和 NLRP3 炎性体介导的细胞焦亡来减轻 PM 诱导的 ALI，这是通过 Nrf2 信号通路介导的。
