Ulinastatin ameliorates LPS‑induced pulmonary inflammation and injury by blocking the MAPK/NF‑κB signaling pathways in rats.

Abstract

Ulinastatin, a urinary trypsin inhibitor (UTI) is commonly used to treat patients with acute inflammatory disease. However, the underlying mechanisms of its anti‑inflammatory effect in acute lung injury (ALI) are not fully understood. The present study aimed to investigate the protective effect of UTI and explore its potential mechanisms by using a rat model of lipopolysaccharide (LPS)‑induced ALI. Rats were treated with 5 mg/kg LPS by intratracheal instillation. The histological changes in LPS‑induced ALI was evaluated using hematoxylin and eosin staining and the myeloperoxidase (MPO) activity was determined using ELISA. The wet/dry ratio (W/D ratio) of the lungs was used to assess the severity of pulmonary edema and Evans blue dye was used to evaluate the severity of lung vascular leakage. The results demonstrated that LPS administration induced histological changes and significantly increased the lung W/D ratio, MPO activity and Evans blue dye extravasation compared with the control group. However, treatment with UTI attenuated LPS‑induced ALI in rats by modifying histological changes and reducing the lung W/D ratio, MPO activity and Evans blue dye extravasation. In addition, LPS induced the secretion of numerous pro‑inflammatory cytokines in bronchoalveolar lavage fluid (BALF), including tumor necrosis factor‑α, interleukin (IL)‑6, IL‑1β and interferon‑γ; however, these cytokines were strongly reduced following treatment with UTI. In addition, UTI was able to reduce cellular counts in BALF, including neutrophils and leukocytes. Western blotting demonstrated that UTI significantly blocked the LPS‑stimulated MAPK and NF‑κB signaling pathways. The results of the present study indicated that UTI could exert an anti‑inflammatory effect on LPS‑induced ALI by inhibiting the MAPK and NF‑κB signaling pathways, which suggested that UTI may be considered as an effective drug in the treatment of ALI.

• Authors: Minjie Ju, Hongyu He, Song Chen, Yimei Liu, Yujing Liu, Simeng Pan, Yijun Zheng, Lizhen Xuan, Duming Zhu, Zhe Luo
• Journal: Molecular medicine reports (Mol Med Rep) Vol. 20 Issue 4 Pg. 3347-3354 (Oct 2019) ISSN: 1791-3004 [Electronic] Greece
• PMID: 31432172 (Publication Type: Journal Article)

Chemical References

• Cytokines
• Glycoproteins
• Lipopolysaccharides
• NF-kappa B
• Peroxidase
• urinastatin

Topics

• Animals
• Cytokines (metabolism)
• Glycoproteins (pharmacology)
• Lipopolysaccharides (toxicity)
• Lung Injury (chemically induced, drug therapy, metabolism, pathology)
• MAP Kinase Signaling System (drug effects)
• Male
• NF-kappa B (metabolism)
• Peroxidase (metabolism)
• Pneumonia (chemically induced, drug therapy, metabolism, pathology)
• Rats
• Rats, Sprague-Dawley