Sodium Butyrate Inhibits the Inflammation of Lipopolysaccharide-Induced Acute Lung Injury in Mice by Regulating the Toll-Like Receptor 4/Nuclear Factor κB Signaling Pathway

Bacterial pneumonia is a common disease in dairy herds worldwide, which brings great economic losses to farmers. Sodium butyrate (SB), an inhibitor of histone deacetylase, plays an important role in limiting inflammation. The purpose of this study was to investigate the protective effects of SB on lipopolysaccharide (LPS)-induced acute lung injury (ALI) in mice and explore the potential mechanism of SB protection. A total of 30 ICR mice were randomly divided into three groups (n = 10): a phosphate-buffered saline (PBS) intratracheal instillation group, a LPS intratracheal instillation group, and a SB gavage group (SB was given 1 h before the LPS stimulation). After 12 h, samples of the blood and lung tissue were collected from the mice for experimental analysis. The results showed that the concentration of inflammatory cytokines [interleukin 1β (IL1β) and tumor necrosis factor α (TNF-α)], myeloperoxidase (MPO) activity in the lung tissue and blood, protein abundance of toll-like receptor 4 (TLR4), nuclear factor κB (NF-κB, p65), phosphorylated p65 (p-p65), inhibitor κBα (IκBα), and phosphorylated IκBα (p-IκBα), and relative mRNA expression of genes associated with inflammation, such as TLR4, NF-κB, IL1β, interleukin 6 (IL6), and TNF-α, were significantly upregulated in the LPS group compared to the PBS group. However, the SB addition markedly downregulated the levels of these parameters in the LSB group compared to those in the LPS group. Furthermore, the structure of the lung tissue from the LPS group was severely disrupted in comparison to that of the PBS group. However, with SB administration, the severe structural disruption was relieved. In addition, an immunohistochemical analysis showed that positive immunoreactions to TLR4, p65, and TNF-α were significant in the LPS group; however, SB addition markedly attenuated this phenomenon. In conclusion, the ALI mouse model was successfully established with an intratracheal instillation of LPS. Furthermore, gavage with SB inhibited inflammation in LPS-induced ALI.