[Role of prostacyclin and thromboxane A2 in pulmonary hyper-permeability induced by mechanical ventilation in...

To explore the role of prostacyclin (PGI2) and thromboxane A2 (TXA2) in lung hyper-permeability induced by mechanical ventilation (MV) in rabbits.

Forty-eight healthy Japanese white rabbits were randomly allocated to vehicle treatment group (group V), tranylcypromine (a PGI2 synthase inhibitor) treatment group (group T), dazoxiben (a TXA2 synthase inhibitor) treatment group (group D), vehicle-treated MV group (group VM), tranylcyprominetreated MV group (group TM) and dazoxiben-treated MV group (group DM). The contents of PGI2 and TXA2 in the lung tissues and TNF-α level in BALF and lung tissues were measured by ELISA. The lung wet/dry weight (W/D) ratio, lung permeability index and pulmonary expressions of myosin light chain kinase (MLCK) protein and mRNA were detected to evaluate the pulmonary permeability. The severities of lung injury were assessed by lung histological scores.

The measured parameters did not differ significantly among the rabbits receiving different treatments without MV. In rabbits in group VM, the contents of PGI2 and TXA2 in the lungs, TNF-α in BALF and lung tissues, PGI2/TXA2 ratio, lung W/D ratio, lung permeability index, pulmonary expressions of MLCK protein and mRNA and histological scores of the lungs all increased significantly (P < 0.05) as compared with those in group V, group T and group D. In rabbits undergoing MV, inhibition of PGI2 production by tranylcypromine significantly decreased the PGI2/TXA2 ratio (P < 0.05), further enhanced the production of TNF-α in the BALF and lung tissue (P < 0.05), and worsened lung hyper-permeability and lung injury (P < 0.05), while treatment with dazoxiben significantly reduced TXA2 production in the lung tissue (P < 0.05), increased the PGI2/TXA2 ratio (P < 0.05) and decreased TNF-α production in the BALF and lung tissue (P < 0.05), thus resulting in alleviated lung hyperpermeability and lung injury (P < 0.05).

PGI2 plays a protective role against MV-induced lung hyper-permeability and lung injury by downregulating TNF-α/MLCK signaling pathway, while TXA2 can exacerbate MV-induced lung hyperpermeability in rabbits by up-regulating TNF-α/ MLCK signaling pathway.