Emergency Department, Beijing Tongren Hospital, Capital Medical University, No. 2, Xihuan South Road, Economic and Technological Development Zone, Daxing District, Beijing, 100176, China.
J Mol Histol. 2024 Oct;55(5):687-698. doi: 10.1007/s10735-024-10222-4. Epub 2024 Jul 23.
BACKGROUND/OBJECTIVES: Sepsis-induced acute lung injury (ALI) is the typical complications of sepsis with a high global incidence and mortality. Inhibition of inflammatory response is a crucial and effective strategy for sepsis-induced ALI. Pedunculoside (PE) has been shown to have an anti-inflammatory effect on various diseases. However, the effect and mechanism of PE on sepsis-induced ALI remain unknown.
MATERIALS/METHODS: A mice model of sepsis-induced ALI was constructed by cecal ligation and puncture (CLP). The effect of PE on the CLP-induced mice were assessed using pathological staining, terminal deoxynucleotidyl transferase deoxyuridine triphosphate (dUTP) nick end labeling (TUNEL), reverse transcription quantitative polymerase chain reaction (RT-qPCR), enzyme-linked immunosorbent assay (ELISA) and western blot assays.
PE reduced pathological symptoms and scores, apoptosis and the W/D ratio of lung tissues in CLP-induced mice. Besides, PE decreased the level of interleukin (IL)-1β, IL-6 and tumor necrosis factor (TNF)-α), pulmonary fibrosis and the expression of fibrosis markers. Mechanically, PE inhibited AKT/NF-κB signaling in CLP-induced mice. Activation of AKT/NF-κB pathway abolished the ameliorative effect of PE on the pathological symptoms, the release of inflammatory factors and pulmonary fibrosis of CLP-induced mice.
PE improved inflammation and pulmonary fibrosis by inhibiting AKT/NF-κB pathway in CLP-induced mice.
背景/目的：脓毒症诱导的急性肺损伤（ALI）是脓毒症的典型并发症，具有较高的全球发病率和死亡率。抑制炎症反应是脓毒症诱导的 ALI 的关键和有效策略。杠柳苷（PE）已被证明对各种疾病具有抗炎作用。然而，PE 对脓毒症诱导的 ALI 的作用和机制尚不清楚。
材料/方法：通过盲肠结扎和穿孔（CLP）构建脓毒症诱导的 ALI 小鼠模型。使用病理染色、末端脱氧核苷酸转移酶 dUTP 缺口末端标记（TUNEL）、逆转录定量聚合酶链反应（RT-qPCR）、酶联免疫吸附测定（ELISA）和 Western blot 分析评估 PE 对 CLP 诱导的小鼠的影响。
PE 减轻了 CLP 诱导的小鼠的病理症状和评分、肺组织的细胞凋亡和 W/D 比值。此外，PE 降低了白细胞介素（IL）-1β、IL-6 和肿瘤坏死因子（TNF）-α）、肺纤维化和纤维化标志物的表达。在机制上，PE 抑制了 CLP 诱导的小鼠中的 AKT/NF-κB 信号通路。激活 AKT/NF-κB 通路消除了 PE 对 CLP 诱导的小鼠的病理症状、炎症因子释放和肺纤维化的改善作用。
PE 通过抑制 CLP 诱导的小鼠中的 AKT/NF-κB 通路改善了炎症和肺纤维化。
