<br>Fortunellin 通过抑制 TLR4/NF-κB/NLRP3 通路来改善 LPS 诱导的急性肺损伤、炎症和胶原蛋白沉积,Immunity, Inflammation and Disease

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Fortunellin 通过抑制 TLR4/NF-κB/NLRP3 通路来改善 LPS 诱导的急性肺损伤、炎症和胶原蛋白沉积
Immunity, Inflammation and Disease ( IF 3.1 ) Pub Date : 2024-03-19 , DOI: 10.1002/iid3.1164
Danjuan Liu ₁ , Rongjie Guo ₁ , Bingbing Shi ₁ , Min Chen ₁ , Shuoyun Weng ₂ , Junting Weng ₁

Affiliation

目的急性肺损伤（ALI）是急性炎症中普遍存在的呼吸系统疾病，发病率和死亡率高。Fortunellin 具有抗炎特性，但它在 ALI 中的作用仍然难以捉摸。因此，本研究阐明了 fortunellin 对 ALI 发病机制的作用。方法通过脂多糖（LPS）诱导建立 ALI 小鼠模型，并利用苏木精-伊红（HE）染色评估肺组织损伤。通过肺湿/干（W/D）比值测量肺组织水肿。肺毛细血管通透性由支气管肺泡灌洗液（BALF）中的蛋白质含量反映。通过评估 BALF 中髓过氧化物酶（MPO）、中性粒细胞和白细胞的含量来测量炎性细胞浸润。通过末端脱氧核苷酸转移酶 dUTP 缺口末端标记（TUNEL）测定法测量细胞凋亡。使用酶联免疫吸附测定（ELISA）测定对炎性细胞因子的分泌进行定量。通过 Masson 染色评估肺组织胶原沉积。结果Fortunellin 减轻了 LPS 诱导的肺组织损伤，降低了 W/D 比值、肺组织中 MPO 含量、BALF 中总蛋白含量以及中性粒细胞和白细胞数量。此外，fortunellin 减轻了 LPS 刺激的肺组织凋亡、炎症反应和胶原蛋白沉积。此外，Fortunellin 抑制了 LPS 刺激的 ALI 模型和 LPS 诱导的 RAW264.7 细胞中 Toll 样受体 4 （TLR4）/核因子 kappa-B （NF-κB）/NLR 家族 Pylin 结构域 3 （NLRP3）通路的活性。此外，fortunellin 通过抑制 TLR4/NF-κB/NLRP3 通路减轻 LPS 刺激的组织损伤、细胞凋亡、炎症和肺胶原沉积。结论Fortunellin 通过抑制 TLR4/NF‐κB/NLRP3 通路减弱 LPS 刺激的 ALI。Fortunellin 可能是 ALI 治疗的宝贵药物。

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Fortunellin ameliorates LPS‐induced acute lung injury, inflammation, and collagen deposition by restraining the TLR4/NF‐κB/NLRP3 pathway

ObjectiveAcute lung injury (ALI) is the prevalent respiratory disease of acute inflammation with high morbidity and mortality. Fortunellin has anti‐inflammation property, but its role in ALI remains elusive. Thus, this study clarified the function of fortunellin on ALI pathogenesis.MethodsThe ALI mouse model was established by lipopolysaccharide (LPS) induction, and lung tissue damage was evaluated utilizing hematoxylin–eosin (HE) staining. The edema of lung tissue was measured by the lung wet/dry (W/D) ratio. The lung capillary permeability was reflected by the protein content in bronchoalveolar lavage fluid (BALF). Inflammatory cell infiltration was measured by the evaluation of the content of myeloperoxidase (MPO), neutrophils, and leukocytes in BALF. Cell apoptosis was measured by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay. The secretions of inflammatory cytokines were quantified using enzyme‐linked immunosorbent assay (ELISA) assays. Lung tissue collagen deposition was evaluated by Masson staining.ResultsFortunellin attenuated LPS‐induced lung tissue damage and reduced the W/D ratio, the content of MPO in lung tissue, the total protein contents in BALF, and the neutrophils and leukocytes number. Besides, fortunellin alleviated LPS‐stimulated lung tissue apoptosis, inflammatory response, and collagen deposition. Furthermore, Fortunellin repressed the activity of the Toll‐like receptor 4 (TLR4)/nuclear factor kappa‐B (NF‐κB)/NLR Family Pyrin Domain Containing 3 (NLRP3) pathway in the LPS‐stimulated ALI model and LPS‐induced RAW264.7 cells. Moreover, fortunellin attenuated LPS‐stimulated tissue injury, apoptosis, inflammation, and collagen deposition of the lung via restraining the TLR4/NF‐κB/NLRP3 pathway.ConclusionFortunellin attenuated LPS‐stimulated ALI through repressing the TLR4/NF‐κB/NLRP3 pathway. Fortunellin may be a valuable drug for ALI therapy.

更新日期：2024-03-19

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