Objective     To identify the effect of high airway pressure caused by mechanical ventilation on the airway mucous hypersecretion in rats.     Methods     Forty-eight Sprague-Dawley rats were randomly divided into f

our groups. After anesthesia and tracheotomy were performed

all rats were challenged with tracheal cannula and received ventilation with small animal ventilator. Control group kept spontaneous breath without mechanical ventilation. Mechanical ventilation group were divided to 10

20 and 30 cmH

2

O airway pressure levels (n=8 for each level) and respectively ventilated for 6 h. Ruthenium red (RR) pre-treatment group were injected with RR via tail vein

an antagonist of transient receptor potential vanilloid 4 (TRPV4) before ventilation. 4-α-Phorbol-12

13-didecanoate (4α-PDD) pre-treatment group were injected with 4α-PDD

an agonist of TRPV4 before ventilation. Rats were sacrificed after ventilation

and their bronchoalvelar lavage fluid (BALF) and lung tissue were collected and stored with common methods. The mucin (MUC) 5AC MUC5AC protein in the BALF was detected by enzyme-linked immunosorbent assay (ELISA)

and its mRNA level in the lung tissues was analyzed by RT-PCR.     Results     Compared with control group

the expression of MUC5AC protein and mRNA were increased in mechanical ventilation group in a pressure-dependent manner

and significantly higher in 30 cmH

2

O airway pressure level than in control group (0.71±0.10 and 6.23±0.54 vs 0.29±0.05 and 1.68±0.35

P0.01). Pretreatment of RR resulted in significantly decreased expression of MUC5AC at protein and mRNA levels in 30 cmH

2

O airway pressure level (0.41±0.06 and 4.15±0.22

P0.05)

but these events were strongly reversed by pretreatment of 4α-PDD (1.12±0.09 and 8.47±0.35

P0.05).     Conclusion     High airway pressure induced by mechanical ventilation can significantly up-regulate MUC5AC at protein and mRNA levels through TRPV4-medicated signal pathway.