Effects of FTY720 pretreatment on ventilator-induced lung injury in rats

Objective To study the effects of FTY720 pretreatment on ventilator-induced lung injury (VILI) in rats in order to explore the role of sphingosine-1-phosphate receptor 1 (S1PR1). Methods Forty healthy adult male SD rats weighing 300-350 g were randomly (randlom number)divided into 4 groups (n=10 each): group CV (conventional tidal volume VT = 8 mL/kg), group HV (high tidal volume VT= 40 mL/kg), group HF and group HFW. The rats in group HF received intra-gastric administration of FTY720 10 mg·kg-1·d-1for 7 days, while additional dose of W146 (S1PR1 antagonist) 1 mg·kg-1·d-1 was administrated in group HFW before high tidal volume ventilation. After 4-hour mechanical ventilation, arterial blood samples were obtained for blood gas analysis before the animals were sacrificed. The lungs were harvested for histopathologic observation. Apoptosis rate in lung tissue was determined with flow cytometry. W/D lung weight ratio, pulmonary permeability index (PPI), total protein, and TNF-α, IL-1β in bronchoaveolar lavage fluid (BALF) were measured. All data were analyzed by one-way analysis of variance (ANOVA), The intergroup comparisons were analyzed by the least-significant-difference (LSD) test by using SPSS version 20.0 software. Differences were considered statistically significant if P<0.05. Results Compared with group CV, the level of PaO2 [(73.6± 8.9) vs.(50.5± 6.0)] was decreased, the levels of W/D [(3.12± 0.27)vs. (5.12± 0.56)], PPI [(0.08±0.03)vs.(0.30 ± 0.06)], apoptosis rate [(10.6±2.9)vs.(48.5±6.7)], total protein [(5.8±2.1)vs.(15.4±5.6)] and TNF-α [(24.3±5.7) vs. (108.4±16.0)] and IL-1β [(90.6±14.1) vs.(338.5±44.3)] were increased in group HV (P 0.05). Compare with group CV, The histopathologic damage of lung tissue was obvious in group HV and group HFW, it was attenuated by pretreatment with FTY720 in group HF. Conclusions FTY720 pretreatment provides protective effects against ventilation-induced lung injury in rats, and S1PR1 may mediate the protection through reducing apoptosis rate and inflammatory reaction. Key words: Receptions, Lysosphingolipid; Respiration, artificial; Respiratory distress syndrome, adult; Apoptosis; Inflammatory response; Rats