Expression Of Protease-activated Receptor-2 In Lung Injury Of Rats With Different Ventilatory Volumes

Objective:To observe the expression of protease-activated receptor-2 (PAR-2) in ventilator-induced lung injury (VILI) of experimental rats with different ventilatory volumes, investigate the relationship between the expression of PAR-2 and VILI.Methods:A total of 60 SD rats were randomly divided into a control group (group A, n=20), a normal tidal volume (VT) group (group L, n=20, VT=8ml/kg), and a hyper-ventilation group of relative larger VT group (group H, n=20, VT=40ml/kg). Rats in groups were randomly divided into 4 subgroups respectively by 0.5h, 1h,2h and 3h. Rats were inserted tracheal catheter via cricothyroid membrane under urethane injection anesthesia, and received different volume of ventilation except the control group. The rats were connected to a volume-controlled ventilator delivering 21% oxygen at a frequency of 40 breaths/min with an inspiratory/expiratory ratio of 1/2, and ventilated at positive end-expiratory pressure (PEEP) of 0 cmH2O. The samples of lung were collected at 0.5h, 1h,2hand 3 h after ventilation. Lung tissue histopathological changes were observed, the wet/dry weight in lung tissue were measured, white blood cell (WBC) in bronchoalveolar lavage fluid (BALF) were counted. The concentrations of tumor necrosis factor-alpha (TNF-alpha) and interleukin-8 (IL-8) in serum was measured with enzyme linked immunosorbent assay (ELISA). The mRNA expression and the protein expression of PAR-2 in lungs were detected by reverse transcription polymerase chain reaction (RT-PCR) and immunohistochemistry at each time point.Results:High-volume mechanical ventilation resulted in substantial lung morphological changes. The interstitial pulmonary edema and pneumorrhagia showed statistical significance in group H when compared with group A and group L (P<0.05). The quantities of WBC in BALF in group H were higher than in group A and L (P<0.05). The concentrations of serum TNF-alpha and IL-8 were signficantly higher than those of A group and L grouop at the same time (P<0.05). In group A there were no PAR-2 mRNA (PAR-2/β-actin) expression, in group L there were small amounts of PAR-2 mRNA exprssion, and PAR-2 mRNA expression increased significantly in group H and it maintained a higher level since then, especially at 3h (P<0.05). The changing trend of the expression of PAR-2 protein was the same as that of PAR-2 mRNA expression (P<0.05). These tendencies were basically positively correlated to lung injury scores and concentrations of TNF-alpha and IL-8.Conclusion:The expression of PAR-2 mRNA and PAR-2 protein increase significantly with high-volume mechanical ventilation, and increase slightly with normal tidal volume. They are positively correlated to lung injury scores.