1.Effect of silicon dioxide exposure on airway surface microenvironment and NEK7/NLPR3 inflammasome in rats
Wenlu HANG ; Qi WU ; Wanjun LI ; Yun BO ; Xianmei ZHOU
Journal of Preventive Medicine 2023;35(2):180-184
Objective:
To examine the effect of SiO2 exposure on the airway surface microenvironment and NIMA-related kinase 7 (NEK7)/nucleotide-binding oligomerization domain-like receptor containing pyrin domain 3 (NLRP3) inflammasome in rats.
Methods:
Twenty-four specific pathogen-free male rats of the SD strain were randomly divided into the control group and the model group, of 12 rats in each group. Rats in the model group were given SiO2 suspensions through disposable tracheal intubation perfusion to model silicosis in rats, while rats in the control group was perfused with the same amount of physiological saline. The pH value and glucose level were measured in the rat bronchoalveolar lavage fluid (BALF) 14 and 28 days after modeling. Lung tissues were stained with HE and Masson and the distribution of inflammatory cells and the deposition of pulmonary interstitial collagens were observed in lung tissues under a light microscope. The expression of transforming growth factor β1 (TGF-β1), collagen type Ⅰ(ColⅠ), collagen type Ⅲ (Col Ⅲ), interleukin-1β (IL-1β), NLRP3, N-terminal domain of Gasdermin D (GSDMD-NT), caspase-1, and NEK7 was quantified in lung specimens using immunohistochemistry.
Results:
Lower pH values were measured in rat BALF in the model group than in the control group 14 [(6.38±0.05) vs. (6.68±0.08), P<0.05] and 28 days after modeling [(6.63±0.14) vs. (6.86±0.05), P<0.05], while higher glucose levels were seen in the model group than in the control group 14 [(0.39±0.06) vs. (0.31±0.04) mg/dL, P<0.05] and 28 days after modeling [(0.39±0.08) vs. (0.31±0.06) mg/dL, P<0.05]. HE and Masson staining showed mild to moderate alveolitis and pulmonary fibrosis in rats 14 days post-exposure to SiO2, and showed moderate to severe alveolitis and pulmonary fibrosis 28 days post-exposure. Immunohistochemistry detected higher TGF-β1, ColⅠ, Col Ⅲ, IL-1β, NLRP3, GSDMD-NT, caspase-1 and NEK7 expression in rat lung tissues in the model group than in the control group (all P<0.05).
Conclusions
SiO2 exposure may cause changes in rat airway surface microenvironment, including BALF acidification and elevated glucose. Pyroptosis induced by activation of NEK7-associated NLRP3 inflammasome may be an important mechanism of pulmonary fibrosis caused by silicosis.
2.Research progress of traditional Chinese medicine extracts in intervention of fibrosis caused by silicosis
Wenlu HANG ; Qi WU ; Ying ZHAO ; Xianmei ZHOU
Journal of Environmental and Occupational Medicine 2022;39(2):229-235
Silicotic nodules and pulmonary fibrosis are histopathological appearance in silicosis patients after long-term inhalation of crystalline silica particles, and are difficult to reverse and recover. Research on the pathogenesis and treatment strategies of silicosis has significantly lagged behind medical progress and clinical needs, resulting in the disease remaining a thorny clinical problem. Traditional Chinese medicine extracts or compound preparations have become a hot issue in exploring silicosis treatment strategies in recent years. This paper described the main pathological processes of pulmonary fibrosis caused by silicosis, followed by introducing its main pathogenesis mechanisms, including transforming growth factor-β1 (TGF-β1)/Smad signaling pathway, oxidative stress reaction, apoptosis, and autophagy. In addition, it briefly described the research progress, targets, and intervention effects of selected traditional Chinese medicine extracts, which provides a scientific basis for the theoretical and clinical research of traditional Chinese medicine extracts in inhibiting pulmonary fibrosis. To change the clinical status quo of silicosis fibrosis which is difficult to control and reverse, the paper proposed that we can further explore the pathogenesis and progression mechanisms of silicosis and drug treatment strategy, and focus on the transformation of basic research into clinical practice.