Hydrogen intervenes early inflammation of silicosis through the NF-κB/NLRP3 signaling pathway / 中国职业医学

ABSTRACT

{L-End}Objective To study the intervention effect of hydrogen on early inflammation in a rat silicosis model and its mechanism. {L-End}Methods Wistar rats of specific pathogen free were randomly divided into the control group, model group, tetrandrine group, hydrogen group and combined intervention group, with 10 rats in each group. The rats in the last four groups were treated with a dose of l.00 mL silica suspension with a mass concentration of 50.0 g/L by a one-time non-exposed tracheal method. The rats in the control group were given 0.9% sodium chloride solution in equal volume. After 24 hours of dust exposure, rats of the tetrandrine group were given 30 mg/kg body mass tetrandrine by gavage daily, rats of the hydrogen group were given 66.6% hydrogen inhalation continuously for four hours daily, rats of the combined intervention group were given the same interventions as the rats in the tetrandrine group and the hydrogen group, rats in the control group and model group were given 0.9% sodium chloride solution in equal volume by gavage. After 14 days of treatment, the lung coefficient of rats was determined, and lung histopathology was performed. The level of malondialdehyde in serum was detected by colorimetry. The level of tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) in serum were detected by enzyme-linked immunosorbent assay. The relative expression of nucleotide-binding oligomerization domain-like receptor thermal protein domain associated protein 3 (NLRP3), nuclear factor-κB (NF-κB) p65, NF-κB phosphorylated p65 (NF-κB p-p65), cysteinyl aspartate specific proteinase1 (Caspase1) and apoptosis-associated speck-like protein containing a CARD (ASC) in serum were detected in lung tissues by Western blot. The relative expression of NLRP3 and NF-κB p65 in lung tissues were detected by immunohistochemistry. {L-End}Results The result of pulmonary histopathology showed that the model group had obvious alveolar rupture and fusion, interstitial lymphocyte and macrophage infiltration, and alveolar wall thickening, collagen fibre deposition, and mild fibrotic hyperplasia, compared with the control group. The pathological outcomes of lung tissues in the three treated groups were alleviated compared with the model group, and the alveolar structure was more complete and the alveolar wall was thinner and the fewer collagen fibres in the rats of combined intervention group, compared with tetrandrine group and hydrogen group. The lung coefficient and Szapiel score of rats of the tetrandrine group, hydrogen group and combined intervention group were lower than those of the model group (all P<0.05). The levels of serum malondialdehyde, TNF-α and IL-1β in lung tissues, and the relative expression of NLRP3, NF-κB p65, NF-κB P-p65, Caspase1 and ASC in lung tissues increased in the model group, compared with the control group (all P<0.05). The indexes above decreased in the three treated groups than those in the model group (all P<0.05). The indexes above decreased in the combined intervention group than those in the tetrandrine group and hydrogen group (all P<0.05), except for the level of malondialdehyde in serum and the relative expression of NF-κB p-p65 in lung tissue. {L-End}Conclusion Hydrogen can intervene the early inflammation of silicosis through NF-κB/ NLRP3 signaling pathway.