Cerebral ischemia/reperfusion injury induces airway mucus hypersecretion in rats and activates IL-13-associated inflammatory mechanisms

The majority of patients that suffer a stroke have excessive sputum, which accelerates the development of pulmonary complications. However, it is unclear whether cerebral ischemia and reperfusion (I/R) injury induces mucus hypersecretion, and the potential role of inflammation remains unknown. In the present study, the reversible middle cerebral artery occlusion model was applied in rats to induce cerebral I/R injury. The rats were grouped according to the duration of reperfusion (6, 12, 24, 48 and 72 h). Neurological dysfunction was evaluated by Longa scoring and lung dry-to-wet weight (dw/ww) ratios were determined to reflect the degree of mucus secretion. Inflammatory factor interleukin-13 (IL-13) and tumor necrosis factor-α (TNF-α) levels in serum and bronchoalveolar lavage fluid (BALF) were determined by enzyme-linked immunosorbent assay. Pulmonary levels of mucin 5AC (MUC5AC) and key molecules involved in nuclear factor-κB (NF-κB) signaling were determined by western blotting and immunohistochemistry. Rats with cerebral I/R had impaired neurological function, which was associated with the length of reperfusion time. In addition, the dw/ww lung ratio decreased and the pulmonary expression of MUC5AC increased with the increase in severity of neurological dysfunction, indicating that cerebral I/R may induce mucus hypersecretion in a reperfusion time-dependent manner. IL-13 and TNF-α levels in serum and BALF, as well as the nuclear translocation of NF-κB p65 in pulmonary tissues, significantly increased following cerebral I/R, which suggests that the activation of IL-13 and NF-κB inflammatory pathways may be involved. The present study concluded that cerebral I/R injury may induce airway mucus hypersecretion by activating IL-13 and NF-κB inflammatory pathways.