福替那韦通过抑制 TLR4/NF-κB/NLRP3 通路改善 LPS 诱导的急性肺损伤、炎症和胶原沉积。
Fortunellin ameliorates LPS-induced acute lung injury, inflammation, and collagen deposition by restraining the TLR4/NF-κB/NLRP3 pathway.
机构信息
Department of Critical Care Medicine, the Affiliated Hospital of Putian University, Putian, China.
School of Ophthalmology & Optometry, Wenzhou Medical University, Wenzhou, China.
出版信息
Immun Inflamm Dis. 2024 Mar;12(3):e1164. doi: 10.1002/iid3.1164.
OBJECTIVE
Acute 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.
METHODS
The 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.
RESULTS
Fortunellin 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.
CONCLUSION
Fortunellin attenuated LPS-stimulated ALI through repressing the TLR4/NF-κB/NLRP3 pathway. Fortunellin may be a valuable drug for ALI therapy.
目的
急性肺损伤（ALI）是一种常见的急性炎症性呼吸道疾病，其发病率和死亡率均较高。 Fortunellin 具有抗炎作用，但它在 ALI 中的作用尚不清楚。因此，本研究阐明了 Fortunellin 对 ALI 发病机制的作用。
方法
采用脂多糖（LPS）诱导建立 ALI 小鼠模型，通过苏木精-伊红（HE）染色评估肺组织损伤，肺湿/干（W/D）比值评估肺组织水肿，支气管肺泡灌洗液（BALF）中蛋白含量反映肺毛细血管通透性，BALF 中髓过氧化物酶（MPO）、中性粒细胞和白细胞含量评估炎症细胞浸润，末端脱氧核苷酸转移酶 dUTP 末端标记（TUNEL）法评估细胞凋亡，酶联免疫吸附试验（ELISA）检测炎症细胞因子的分泌，Masson 染色评估肺组织胶原沉积。
结果
Fortunellin 减轻 LPS 诱导的肺组织损伤，降低 W/D 比值、肺组织 MPO 含量、BALF 总蛋白含量以及中性粒细胞和白细胞数量。此外， Fortunellin 减轻 LPS 刺激的肺组织凋亡、炎症反应和胶原沉积。此外， Fortunellin 抑制 LPS 刺激的 ALI 模型和 LPS 诱导的 RAW264.7 细胞中的 Toll 样受体 4（TLR4）/核因子 kappa-B（NF-κB）/NLR 家族 Pyrin 域包含 3（NLRP3）通路活性。而且， Fortunellin 通过抑制 TLR4/NF-κB/NLRP3 通路减轻 LPS 刺激的肺组织损伤、凋亡、炎症和胶原沉积。
结论
Fortunellin 通过抑制 TLR4/NF-κB/NLRP3 通路减轻 LPS 刺激的 ALI。 Fortunellin 可能是治疗 ALI 的有价值药物。
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