Effects Of Sea Cucumber Polypeptide On Pulmonary Fibrosis In SD Rats

Pulmonary fibrosis is the terminal manifestation of a large class of pulmonary diseases.Its clinical features are decreased lung function and progressive dyspnea,which are irreversible and mainly related to alveolar epithelial cell damage,inflammation,and epithelial-mesenchymal transition.Mechanistically,it has similar pathways and targets to cancer.In addition to lung transplantation,the commonly used clinical drugs are pirfenidone and nintedanib,but they have serious side effects and poor prognosis.Sea cucumber is a precious food homologous food.Studies have shown that sea cucumber peptide(SCP)has potential benefits,such as anti-inflammatory,anticancer,and immune regulation.Therefore,it is of great significance to explore the effect of SCP on pulmonary fibrosis.In the present study,a rat model of pulmonary fibrosis was induced by bleomycin to explore the effect of dietary supplementation of SCP on SD rats’ pulmonary fibrosis.During the 28 days experiment,the low,medium and high doses of SCP were 100,200,and 400 mg/kg BW,respectively.The results showed that:(1)Low and medium doses of SCP significantly reduced the level of IL-1β in lung tissue of rats,by 32.07%and 25.36%,respectively;low dose of SCP significantly(P<0.01)reduced the level of IL6 in lung tissue,decreased by 17.82%;both high,medium and low doses of SCP significantly reduced the level of TNF-α in lung tissue(P<0.01),by 33.99%,23.36%,and 18.30%,respectively;Extremely significant(P<0.01),decreased by 14.89%and 20.55%,respectively,and the high-dose group was significantly(P<0.05)decreased by 8.82%.The low-dose and the middle-dose SCP were extremely reduced the level of αSMA in lung tissue(P<0.01),which were reduced by 15.34%and 23.69%,respectively,and the high-dose group was significantly(P<0.05)reduced by 8.48%.High,medium and low doses of SCP were significantly(P<0.01)reduced the level of VIM in lung tissue by 42.97%,46.41%,and 38.38%,respectively.(2)Histomorphological results showed that SCP improved the damage of lung tissue structure caused by pulmonary fibrosis,including the amelioration of alveolar wall rupture,inflammatory cell infiltration,fibroblast proliferation,deposition of intercellular matrix and collagen fibers.The lung tissues of the rats in the model group and the middle-dose group were selected for metabolomics analysis.The results showed that SCP significantly downregulated the levels of catechol,N-acetyl-L-histidine,acetylcarnitine,stearyl in the lung tissue of rats.Acyl carnitine,D-mannose,L-threonine,L-alanine,glycine,3guanidinopropionic acid,prostaglandin D2,embelic acid D(-)-beta-hydroxybutyric acid levels.KEEG pathway analysis showed that SCP mainly intervenes in pulmonary fibrosis through the lysosomal pathway,in which D-mannose is a key factor.In conclusion,SCP can significantly improve pulmonary fibrosis in rats by reducing the levels of IL-1β,IL-6,TNF-α,α-SMA,and VIM in lung tissue,downregulating the content of serum TGF-β1,and intervening the lysosomal pathway.