Mechanisms involved in inflammatory pulmonary fibrosis induced by lunar dust simulant in rats

摘要

Lunar dust is one of the biggest risk factors in the future manned exploration mission. Much is not known about the pulmonary toxicity of lunar dust. The aim of this study was to evaluate the lung inflammation and oxidative stress induced by subacute exposure to lunar dust stimulant (LDS) in rats. Wistar rats were intratracheally administered LDS, twice a week for 3 weeks. Inflammatory cell counting and cytokine assays using bronchoalveolar lavage fluid (BALF) were performed. Lung tissues were processed for histopathological examination and immunohistochemical staining. Biomarkers of oxidative stress and genes and proteins related to inflammation and fibrosis in lung tissue were also determined. The neutrophil count in the BALF of LDS-exposed groups was higher than that in controls (P < .05). LDS caused a significant increase in some of biochemical indicators and proinflammatory factors levels in BALF compared with control group. The normal balance between oxidation and antioxidation was broken by LDS. Pathological characteristics of lung tissue and immunohistochemical results for alpha-smooth muscle actin (alpha-SMA) indicated that inflammatory response was an extremely important passage to pulmonary fibrosis. Real-time PCR analysis showed elevated levels of nitric oxide synthase (NOS) and nicotinamide adenine dinucleotide phosphate oxidase (NOX) mRNA in the lungs (P < .05). Western blotting results were consistent with immunohistochemistry and qPCR results. These results indicate that inhalation of lunar dust may cause inflammatory pulmonary fibrosis. NOX4 may be a key potential therapeutic target for inflammatory injury and fibrosis in the lung.