Chronic intermittent hypoxia decreases pulmonary clearance of ^99mTc-labelled particulate matter in mice

Obstructive sleep apnea-hypopnea syndrome (OSAHS) could cause systematic inflammation including pulmonary inflammatory response, whereas the influence of OSAHS in pulmonary clearance ability remains unknown. The main pathophysiological feature of OSAHS is chronic intermittent hypoxia (CIH). The goal of this study is to clarify the airway clearance of particulate matter (PM) in CIH mice, and to explore the potential mechanism.

Balb/c mice were divided into a CIH group and a control group, exposed to intermittent hypoxia and air chamber, respectively. A radioactive probe, ^99mTc labeled PM, was endotracheally inserted into the mice at 10 mg/kg, with a starting dose of 800 μCi. The change of radioactive dose reserved in the lung was observed using single-photon emission computed tomography/computed tomography (SPECT/CT) and reconstructed data were analyzed. Special airway resistance (sRaw) of mice was measured by non-invasive airway mechanics sites. Lung resistive load (R_L), elastic resistance, and compliance were measured by a multichannel physiological signal system. Lung injury was judged by hematoxylin-eosin staining and histologic score. Change in mucus secretion was determined using periodic acid-Schiff staining and enzyme-linked immunosorbent assay. Fresh lung tissue was used for real-time polymerase chain reaction and western blot analysis to explore related change of inflammation and signaling molecules and potential mechanical pathway.

Mice in the CIH group had higher PM radioactive deposit than the control group (93.37±3.44 μCi vs. 65.98±2.61 μCi). The average radiation dose in the lung was elevated (0.0005 μCi/mm³ vs. 0.0001383 μCi/mm³). Mice in the CIH group have higher value of sRaw, R_L, and elastic resistance, whereas pulmonary compliance decreased compared to the control group (2.13±0.29 mL/cmH₂O vs. 5.37±1.02 mL/cmH₂O). The CIH group showed a higher histopathological score. Several genes associated with mucin secretion such as chemokine (C-X-C motif) ligand 1 (CXCL1), Clara Cell Secretory Protein 16 (CC16), macrophage inflammatory protein 2 (MIP-2), chloride channel regulator 1 (Gob5), and mucin 5AC (MUC5AC) showed elevated expression. Phosphatidylinostol-3-kinase/serine/threonine-specific protein kinase (PI3K/AKT) pathway was activated in the CIH group.

CIH decreased pulmonary clearance of PM and increased lung airway resistance, which may be related to inflammatory response and mucus hypersecretion in the lung.