[Pathogenic role of leukotriene B4 in pulmonary microvascular endothelial cell hyper- permeability induced by one lung ventilation in rabbits].

OBJECTIVE: To elucidate the pathogenic role of leukotriene B4 (LTB4) in increased pulmonary microvascular endothelial cell permeability induced by one lung ventilation (OLV) in rabbits.

METHODS: Forty-eight healthy Japanese white rabbits were randomly divided into control group (group C), saline pretreatment group (group S), bestatin (a leukotriene A4 hydrolase (LTA4H) inhibitor) plus saline pretreatment group (group B), OLV group (group O), saline pretreatment plus OLV group (group SO) and bestatin plus saline pretreatment with OLV group (group BO). ELISA was used to detect LTB4 content in the lung tissues, and LTA4H and phospholipase Cεl (PLCEl) expressions were examined by Western blotting and quantitative PCR. The wet/dry weight (W/D) ratio of the lung, lung permeability index and the expressions of myosin light chain kinase (MLCK) protein and mRNA in the lung tissues were determined to evaluate the permeability of the pulmonary microvascular endothelial cells (PMVECs). The severities of lung injury were evaluated by lung histomorphological scores.

RESULTS: No significant differences were found among groups C, S and B except that LTA4H expressions was significantly lower in group B than in groups C and S (P<0.05). OLV significantly increased the expressions of LTA4H (P<0.05) and resulted in LTB4 overproduction in the lungs (P<0.05) accompanied by significantly enhanced PLCE1 expression and PMVEC permeability (P<0.05). Pretreatment with bestatin, significantly reduced the expression of LTA4H and LTB4 production (P<0.05) and down-regulated the expression of PLCE1 in the lungs of the rabbits receiving OLV (P<0.05).

CONCLUSION: Bestatin plays a protective role in OLV-induced rabbit lung injury by downregulating LTA4H to reduce the production of LTB4 in the lungs. LTB4 can increase PMVEC permeability by up-regulating PLCE1 expression in rabbits with OLV-induced lung injury.