The Influence Of Silica Dust On Airway Structure And Mucin 5b Expression In Mice

Objective: To explore the influence of silica dust on airway structure and MUC5 B expression in mice.Method: In this study,we established silica dust exposing model by intratracheally instilling silica dust to mice.A total of 72 male C57BL/6 mice were randomly into three groups: blank control group,saline group and silica dust group.The blank control group had no treatment,whereas the saline group and silica dust group were treated with 50 ?l volume of sterile saline and 50 mg/ml silica dust suspension by single intratracheal instillation respectively.Six mice were randomly sacrificed in each group 1,7,28 and 84 days after treatment.The middle lobe of right lungs was fixed in 4% paraformaldehyde and dyed by kinds of staining after paraffin embedding procedure.The changes of mucociliary system structure in trachea and bronchial structure in lung tissue were evaluated by hematoxylin and eosin(HE),alcian-bule/periodic acid Schiff staining(AB-PAS)and Masson staining.The cilia ultrastructure was examined by transmission election microscopy,the expression of MUC5 B mucin in trachea and lung was determined by immunohistochemistry and Western blotting.Result:(1)In blank control and saline groups,the structures of trachea and lung tissues in mice were normal.The ultrastructure of motile cilia on surface of trachea such as microtubules and basal body were intergrated and arranged neatly,the polarity of the central microtubules and the direction of basal foot both pointed to one direction,the submucosal glands structure were normal with very few mucins.In silica group,the structure of trachea and lung tissues of mice was also normal,and the ultrastructure of cilia without obvious changes on day 1.The cilia on surface of trachea mucosal appeared adhesion and lodging,the central microtubules polarity and the direction of the base foot was disorder in parts of cilia,and a number of cilia fusion to form a huge cilia was observed;it was observed that thickened bronchial walls and alveolar septum,narrowed lumens,infiltration of a large number of inflammatory cells and secreted mucins were presented in lung tissues on day 7.The number of cilia on the surface of the main tracheal decreased,the microtubules polarity and the direction of the basal foot were disordered obviously,meanwhile,the number of basal foot decreased,partial cilia microtubules disappeared or the central microtubules was missing,the submucosal gland hyperplasia and contains a lot of mucin;the small fiber band was obsverved around the bronchial and alveolar wall,and inflammatory secretions was accumulated in bronchial lumen and alveolar cavity in lung tissues on day 28.The number of cilia on the surface of trachea decreased greatly,the microtubules structure was almost indistinguishable and couldn't determine the central microtubule polarity,the number of basal foot decreased continuously;The area of fibrosis increased and bronchial walls and alveolar septum became more thicker on day 28,the scores of pathological sections of lung tissues stained with HE and Masson have significant differences compared with control groups(P<0.01).(2)In addition,the mucin of MUC5 B was mainly located in the submucosal glands of trachea and mucous membrane layer of bronchi and alveolar septum.The expression of MUC5 B in trachea and lung tissues gradually increased when exposed to silica dust from day 1 to day 28.However,the MUC5 B level,reduced a little degree on day 84,which was also significant higher than that in blank control and saline group(P<0.01).Conclusion: Silica dust is able to disrupt the ultrastructure of cilia on the surface of trachea and induce the submucosal glands hyperplasia with excessive mucus secretion.Meanwhile,silica dust can result in thickened bronchial walls,narrowed lumen,marked inflammatory varying degrees of fibrosis.Also,silica dust can significantly increase the expression of MUC5 B in trachea and lung tissue in mice.