The role of autophagy in pulmonary inflammatory response in silicosis model rats / 中国职业医学

ABSTRACT

@#Objective To evaluate the role of autophagy in inflammatory response in the lungs of silicosis rats. Methods The specific pathogen-free healthy male Wistar rats were randomly divided into four groups with 10 rats in each group. The rats in the control group were given an equal volume of 0.9% sodium chloride solution; all rats in the silicon dioxide (SiO2 ) group, the SiO2 + 3-methyladenine (3-MA) group, and the SiO2 +rapamycin (RAPA) group were given a mass concentration of 0.05 mg/L of SiO2 suspension (1.0 mL/rat) to establish a rat model of silicosis using non-exposed tracheal instillation method. Two days before SiO2 exposure, the rats in SiO2 +3-MA group were intraperitoneally injected with 3-MA at a dose of 2.5 mg/kg body weight. The rats in the SiO2 +RAPA group were intraperitoneally injected with a dose of RAPA 1.0 mg/kg body weight, once a day, and once every other day after modeling, for a total of 10 injections. The pathological changes in the lung tissue of the rats in each group were evaluated using hematoxylin-eosin and Masson staining. The relative expression levels of transforming growth factor-β (TGF-β) , interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) in the lung tissue of the rats in each group were detected using enzyme-linked immunosorbent assay. The relative expression levels of microtubule-associated protein 1 light chain 3 (LC3) and yeast autophagy-related gene 6 (Beclin1) in lung tissue of rats in each group were detected by Western blotting. Results The pathological observation of rat lung tissue showed that scattered inflammatory nodules and interstitial inflammatory cells were found in the lung tissue of the rats in the SiO2 group. In the SiO2 +3-MA group, the inflammation in the lung tissue was more severe and the alveolar cavity had viscous secretions. The rats in the SiO2 +RAPA group had less inflammation and smaller inflammatory nodules than the SiO2 group. Compared with the control group, the TNF-α, IL-1β, TGF-β, Beclin1 protein relative expression levels and LC3 Ⅱ/Ⅰ ratio in the lung tissue were increased in the SiO2 group (all P<0.05). Compared with the SiO2 group, the relative expression levels of TGF-β and TNF-α in the lung tissue of the rats increased (all P<0.05), and the ratio of LC3 Ⅱ/Ⅰ and Beclin1 protein relative expression decreased in the SiO2+3-MA group (all P<0.05). Compared with the SiO2+ 3-MA group, the relative expression levels of TNF- α, IL-1β and TGF- β in the lung tissue of the SiO2 +RAPA group were decreased (all P<0.05), and the LC3Ⅱ/Ⅰ ratio and the relative expression level of Beclin1 protein were increased (all P<0.05). Conclusion Autophagy occurs when inflammatory reaction occurs in the lungs of silicosis model rats; autophagy has inhibitory effect on pulmonary inflammation.