人参酚通过 Keap1-Nrf2/HO-1 通路减轻 LPS 诱导的小鼠急性肺损伤的铁死亡,Journal of Translational Medicine

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人参酚通过 Keap1-Nrf2/HO-1 通路减轻 LPS 诱导的小鼠急性肺损伤的铁死亡
Journal of Translational Medicine ( IF 6.1 ) Pub Date : 2021-03-02 , DOI: 10.1186/s12967-021-02745-1
Jiucui Li ₁ , Kongmiao Lu ₁ , Fenglan Sun ₁ , Shanjuan Tan ₁ , Xiao Zhang ₁ , Wei Sheng ₁ , Wanming Hao ₁ , Min Liu ₁ , Weihong Lv ₁ , Wei Han ₁

Affiliation

急性肺损伤 (ALI)/急性呼吸窘迫综合征 (ARDS) 可诱发不受控制和自我放大的肺部炎症，并且在危重患者中具有较高的发病率和死亡率。近年来，据报道，许多从草药中提取的生物活性成分可通过不同的机制有效改善 ALI/ARDS。铁死亡被归类为调节性坏死，比细胞凋亡更具免疫原性，并有助于 ALI 的进展。在这项研究中，我们研究了从人参根中分离的人参酚 (PX) 对小鼠脂多糖 (LPS) 诱导的 ALI 的影响。在体内，通过测定 LPS 诱导的肺部炎症、肺水肿和铁死亡来测试 PX 对 LPS 诱导的小鼠 ALI 的作用。体外，BEAS-2B 细胞用于通过确定炎症、铁死亡及其关系来研究 PX 发挥作用的分子机制。给予 PX 保护小鼠免受 LPS 诱导的 ALI，包括显着改善肺病理变化，并降低肺水肿、炎症和铁死亡的程度。在体外，PX 在支气管上皮细胞系 BEAS-2B 细胞中抑制 LPS 诱导的铁死亡和炎症。研究了铁死亡和炎症之间的关系。结果表明，铁死亡介导了 LPS 处理的 BEAS-2B 细胞的炎症，而 PX 可能通过抑制铁死亡来改善 LPS 诱导的炎症。同时，PX 可以上调 Keap1-Nrf2/HO-1 通路，并且选择性抑制 Keap1-Nrf2/HO-1 通路显着消除了 PX 在 LPS 处理的细胞中的抗铁死亡和抗炎功能。PX 通过 Keap1-Nrf2/HO-1 通路减轻 LPS 诱导的 ALI 的铁死亡，是一种有前途的 ALI 新治疗候选药物。

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Panaxydol attenuates ferroptosis against LPS-induced acute lung injury in mice by Keap1-Nrf2/HO-1 pathway

Acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) induces uncontrolled and self-amplified pulmonary inflammation, and has high morbidity and mortality rates in critically ill patients. In recent years, many bioactive ingredients extracted from herbs have been reported to effectively ameliorate ALI/ARDS via different mechanisms. Ferroptosis, categorized as regulated necrosis, is more immunogenic than apoptosis and contributes to the progression of ALI. In this study, we examined the impact of panaxydol (PX), isolated from the roots of Panax ginseng, on lipopolysaccharide (LPS)-induced ALI in mice. In vivo, the role of PX on LPS-induced ALI in mice was tested by determination of LPS-induced pulmonary inflammation, pulmonary edema and ferroptosis. In vitro, BEAS-2B cells were used to investigate the molecular mechanisms by which PX functions via determination of inflammation, ferroptosis and their relationship. Administration of PX protected mice against LPS-induced ALI, including significantly ameliorated lung pathological changes, and decreased the extent of lung edema, inflammation, and ferroptosis. In vitro, PX inhibited LPS-induced ferroptosis and inflammation in bronchial epithelial cell line BEAS-2B cells. The relationship between ferroptosis and inflammation was investigated. The results showed that ferroptosis mediated inflammation in LPS-treated BEAS-2B cells, and PX might ameliorate LPS-induced inflammation via inhibiting ferroptosis. Meanwhile, PX could upregulate Keap1-Nrf2/HO-1 pathway, and selective inhibition of Keap1-Nrf2/HO-1 pathway significantly abolished the anti-ferroptotic and anti-inflammatory functions of PX in LPS-treated cells. PX attenuates ferroptosis against LPS-induced ALI via Keap1-Nrf2/HO-1 pathway, and is a promising novel therapeutic candidate for ALI.

更新日期：2021-03-02

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