| Objective(s): To explore the protective effect and mechanism of sevoflurane and propofol against lung injury induced by mechanical ventilation(MV)from arachidonic acid metabolic COX-2 and 5-LOX pathways.Methods: Forty healthy 8-week-old Sprague Dawley(SD)rats of either sex,weighing 250-300 g,were randomly divided into propofol+ "lung protective" MV group(PP group),propofol+ "injurious" MV group(PI group),Sevoflurane+ "lung protective" MV group(SP group)and sevoflurane+ "injurious" MV group(SI group).In PP group and PI group,anesthesia was maintained by continuous intravenous infusion of propofol at a rate of 3 mg/kg/h(1/3ED95),while SP group and SI group were maintained by 1.2 % sevoflurane(1/3ED95).According to their respective groups,rats were subjected to "lung protective" MV(VT =7m L/kg,PEEP = 5cm H2O)or "injurious" MV(VT = 20 ml/kg,PEEP = 0 cm H2O)for 2 hours.Western-blot(WB)and real-time fluorescence quantitative q PCR(QCPR)were used to detect the expressions of cyclooxygenase-2(COX-2)and 5-Lipoxygenase(5-LOX)in lung tissue.Enzyme linked immunosorbent assay(ELISA)was used to determine the contents of prostacycline I2(PGI2),thromboxane A2(TXA2)and leukotriene B4(LTB4)in lung tissue.Lung permeability index(LPI),lung wet/dry weight(W/D)ratio and lung histological scores were used to reflect the severity of lung injury.Result:1.The expression levels of COX-2 and 5-LOX and the contents of PGI2,TXA2 and LTB4 in lung tissues Compared with “ lung protective” MV groups(PP group and SP group),the expressions of COX-2 and 5-LOX and the contents of PGI2,TXA2 and TLB4 in lung tissues in “ injurious” MV groups(PI group and SI group)were significantly increased(P < 0.05).Under the same MV mode.the above five indicators in propofol treated rats(PP group and PI group)were significantly lower than those in sevoflurane-treated rats(SP group and SI group)(P<0.05).2.Lung W/D weight ratio,lung permeability index and histological scores Lung W/D weight ratio,lung permeability index and lung histological scores in“injurious” MV groups(PI group and SI group)were significantly higher than those in “lung protective” MV groups(PP group and SP group)(P<0.05).In the PI group and SI group,the above-mentioned evaluation indexes of lung injury in PI group were significantly lower than those in SI group(P<0.05).In the PP group and SP group,the lung permeability index in PP group was significantly lower than that in SP group(P<0.05),but not lung W/D ratio and lung histological scores.Conclusion(s):1.Propofol plays a protective role in MV-induced lung injury by downregulating COX-2 and 5-LOX to reduce inflammatory AA metabolites.2.At the equivalent dose of 1/3ED95,propofol has a better protective effect against MV-induced lung injury than sevoflurane,which is related to a more significant reduction in PGI2,TXA2,and LTB4 productions by futher downregulating COX-2and 5-LOX. |