Department of Pharmacy, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong 250021, China.
Oxid Med Cell Longev. 2022 Jun 6;2022:7832983. doi: 10.1155/2022/7832983. eCollection 2022.
Paraquat (PQ), a highly toxic herbicide and primary attack for lung, results in severe acute lung injury (ALI) appeared as evident oxidative stress, inflammation, and apoptosis. Increasing evidence elucidates that nuclear factor erythroid-2-related factor 2 (Nrf2) and its associated nuclear factor-B (NF-B) exhibit many merits for protection of ALI by coordinating a fine-turned response to oxidative stress, inflammation, and apoptosis. Ginkgolide C (GC) has been reported to be a safe and potent therapeutic agent against ALI. However, whether GC could protect ALI induced by PQ poisoning and the possible underlining mechanisms have remained not to be fully elucidated. A rat model of ALI and a model of acute type II alveolar epithelial cell (RLE-6TN) injury constructed by exposure to PQ were applied to discuss the protective effect of GC. Furthermore, Nrf2 gene silencing RLE-6TN cells were used to discuss the exact mechanism. We confirmed that GC significantly ameliorated the histopathological damages, ultrastructural changes, lung injury score, W/D ratio, and Hyp activity of lung tissue and inhibited polymorphonuclear neutrophil (PMN) infiltration after PQ poisoning. Further results revealed that GC remarkably activated Nrf2-based cytoprotective system and inhibited NF-B-induced inflammatory injury as well as apoptosis. Taken together, we concluded that GC preserved protection of PQ-induced ALI via the Nrf2-NF-B dependent signal pathway, which may provide us novel insights into the treatment strategies for PQ poisoning.
百草枯（PQ）是一种剧毒除草剂，主要攻击肺部，导致严重的急性肺损伤（ALI），表现为明显的氧化应激、炎症和细胞凋亡。越来越多的证据表明，核因子红细胞 2 相关因子 2（Nrf2）及其相关核因子-B（NF-B）通过协调对氧化应激、炎症和细胞凋亡的精细反应，为保护 ALI 发挥了许多作用。银杏内酯 C（GC）已被报道是一种安全有效的治疗急性肺损伤的药物。然而，GC 是否能保护 PQ 中毒引起的 ALI，以及可能的潜在机制仍未完全阐明。本研究采用 PQ 中毒诱导的大鼠 ALI 模型和急性Ⅱ型肺泡上皮细胞（RLE-6TN）损伤模型，探讨 GC 的保护作用。进一步使用 Nrf2 基因沉默 RLE-6TN 细胞探讨其确切机制。结果表明，GC 能显著改善 PQ 中毒后的组织病理学损伤、超微结构改变、肺损伤评分、肺组织湿/干重比和 Hyp 活性，抑制多形核中性粒细胞（PMN）浸润。进一步的结果表明，GC 能显著激活 Nrf2 依赖的细胞保护系统，抑制 NF-B 诱导的炎症损伤和细胞凋亡。综上所述，GC 通过 Nrf2-NF-B 信号通路对 PQ 诱导的 ALI 具有保护作用，为 PQ 中毒的治疗策略提供了新的思路。
