Affiliation:
1. Department of Critical Care Medicine the Affiliated Hospital of Putian University Putian China
2. School of Ophthalmology & Optometry Wenzhou Medical University Wenzhou China
Abstract
AbstractObjectiveAcute 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.