Department of Respiratory and Critical Care Medicine, Third People's Hospital of Yuxi City, Yuxi, Yunnan, 653100, China.
Department of Neurology, Third People's Hospital of Yuxi City, Yuxi, Yunnan, 653100, China.
BMC Pharmacol Toxicol. 2024 Sep 6;25(1):63. doi: 10.1186/s40360-024-00787-x.
The impact of Sodium Houttuyniae (SH) on lipopolysaccharide (LPS)-induced ALI has been investigated extensively. However, it remains ambiguous whether ferroptosis participates in this process. This study aimed to find out the impacts and probable mechanisms of SH on LPS-induced ferroptosis. A rat ALI model and type II alveolar epithelial (ATII) cell injury model were treated with LPS. Enzyme-linked immunosorbent assay (ELISA), hematoxylin-eosin (HE) staining, and Giemsa staining were executed to ascertain the effects of SH on LPS-induced ALI. Moreover, Transmission electron microscopy, Cell Counting Kit-8 (CCK8), ferrous iron colorimetric assay kit, Immunohistochemistry, Immunofluorescence, Reactive oxygen species assay kit, western blotting (Wb), and qRT-PCR examined the impacts of SH on LPS-induced ferroptosis and ferroptosis-related pathways. Theresults found that by using SH treatment, there was a remarkable attenuation of ALI by suppressing LPS-induced ferroptosis. Ferroptosis was demonstrated by a decline in the levels of glutathione peroxidase 4 (GPX4), FTH1, and glutathione (GSH) and a surge in the accumulation of malondialdehyde (MDA), reactive oxygen species (ROS), NOX1, NCOA4, and Fe, and disruption of mitochondrial structure, which were reversed by SH treatment. SH suppressed ferroptosis by regulating TRAF6-c-Myc in ALI rats and rat ATII cells. The results suggested that SH treatment attenuated LPS-induced ALI by repressing ferroptosis, and the mode of action can be linked to regulating the TRAF6-c-Myc signaling pathway in vivo and in vitro.
鱼腥草（SH）对脂多糖（LPS）诱导的急性肺损伤（ALI）的影响已经得到了广泛的研究。然而，铁死亡是否参与这一过程仍不清楚。本研究旨在探讨 SH 对 LPS 诱导的铁死亡的影响及其可能的机制。用 LPS 处理大鼠 ALI 模型和 II 型肺泡上皮（ATII）细胞损伤模型。酶联免疫吸附试验（ELISA）、苏木精-伊红（HE）染色和吉姆萨染色用于确定 SH 对 LPS 诱导的 ALI 的影响。此外，透射电子显微镜、细胞计数试剂盒-8（CCK8）、亚铁比色测定试剂盒、免疫组织化学、免疫荧光、活性氧（ROS）测定试剂盒、western blot（Wb）和 qRT-PCR 检测了 SH 对 LPS 诱导的铁死亡和铁死亡相关途径的影响。结果发现，通过使用 SH 处理，通过抑制 LPS 诱导的铁死亡，显著减轻了 ALI。铁死亡通过降低谷胱甘肽过氧化物酶 4（GPX4）、FTH1 和谷胱甘肽（GSH）的水平和增加丙二醛（MDA）、活性氧（ROS）、NOX1、NCOA4 和 Fe 的积累以及破坏线粒体结构来证明，这些变化都被 SH 处理所逆转。SH 通过调节 TRAF6-c-Myc 在 ALI 大鼠和大鼠 ATII 细胞中抑制铁死亡。结果表明，SH 处理通过抑制铁死亡减轻 LPS 诱导的 ALI，其作用方式可以与体内和体外调节 TRAF6-c-Myc 信号通路有关。
