Protective effects of ulinastatin on rats with acute lung injury induced by lipopolysaccharide

Abstract

We aimed to evaluate the protective effects of ulinastatin (UTI) on rats with acute lung injury induced by lipopolysaccharide (LPS) via the Toll like receptor 4 (TLR4)/myeloid differentiation factor 88 (MyD88)/nuclear factor-kappa B (NF-κB) signaling pathway. Forty-eight male Wistar rats were randomly divided into model, control, dexamethasone (DXM) and UTI groups. The body weight loss ratio and wet-to-dry weight ratio (W/D) of lung tissue were calculated at 10 h. The permeability of pulmonary vascular endothelium was detected by Evans blue method. Tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and IL-1β levels in bronchial lavage fluid were detected by enzyme-linked immunosorbent assay. Total cells and neutrophils were counted by microscopy. TLR4, MyD88 and NF-κB expressions were detected by Western blotting. Compared with model group, DXM and UTI 2 groups had significantly higher body weights and lower W/D values (P<0.05). In DXM and UTI groups, the lung tissue structure was close to normal, inflammatory cell infiltration was alleviated, and hematoxylin-eosin staining scores were significantly lower than that of model group (P<0.05). Compared with model group, the concentrations of Evans blue, IL-1β, IL-6 and TNF-α levels, and protein expressions of TLR4, MyD88 and NF-κB in DXM and UTI groups decreased significantly (P<0.05). UTI inhibits LPS-induced activation of the TLR4/MyD88/NF-κB signaling pathway, thereby alleviating inflammatory response and protecting against lung injury.

Suppression of NOD-like receptor protein 3 inflammasome activation and macrophage M1 polarization by hederagenin contributes to attenuation of sepsis-induced acute lung injury in rats

“…Upon stimulation, IκBα is phosphorylated and then dissociated from the NF-κB complex, which liberate NF-κB to the nucleus and activate NF-κB target inflammatory genes. Inhibition of NF-κB pathway has been reported to alleviate ALI [ 56 ] [PMID: 34,637,694]. Recent research has reported that HG treatment alleviated ischemia/reperfusion injury by inhibiting the NF-κB pathway [ 49 ] [PMID: 32,848,779].…”

Ulinastatin promotes macrophage efferocytosis and ameliorates lung inflammation via the ERK5/Mer signaling pathway

“…Ju et al [26] found that UTI improved lung inflammation and injury in rats by inhibiting neutrophil activation, reducing inflammatory cell infiltration, and downregulating inflammatory cytokines. Similarly, Lu et al [27] showed that UTI inhibited LPS-induced activation of the TLR4/MyD88/NF-jB signaling pathway, thereby reducing inflammation and preventing lung injury. Moreover, Hang et al [28] found that UTI exerted lung protection by up-regulating the expression of aquaporin in a porcine acute respiratory distress syndrome two-hit model.…”

“…Similarly, Lu et al. [ 27 ] showed that UTI inhibited LPS‐induced activation of the TLR4/MyD88/NF‐κB signaling pathway, thereby reducing inflammation and preventing lung injury. Moreover, Hang et al.…”

Alanyl-Glutamine (Ala-Gln) Ameliorates Dextran Sulfate Sodium (DSS)-Induced Acute Colitis by Regulating the Gut Microbiota, PI3K-Akt/NF-κB/STAT3 Signaling, and Associated Pulmonary Injury

“…36 Ala-Gln has a protective effect on acute pulmonary injury induced by lipopolysaccharide in rats. 37 Studies have shown that prophylactic inhalation of Ala-Gln can enhance the synthesis of HSP72 and alleviate tissue damage in experimental pulmonary injury. 30 It is well known that the inflammatory immune response mediated by CD4 + T cells is related to the pathogenesis of UC.…”