Abstract: Objective To compare and observe the effects of different levels of phospholipase C epsilon- 1 (PLCE l) expression on the expression of cytoplasmic phospholipase A2 (C-PL2) and its metabolic products in lung tissue of rats undergoing mechanical ventilation (MV), and to elucidate the role of phospholipase C epsilon-1(PLCE l) in MV- induced increased permeability of pulmonary microvascular endothelial cells (PMEC). 
Methods Twenty-four 8-10 week-old SPF rats (weighing 180-200 g) with an equal number of males and females were randomized equally into wild-type rats+"lung protective" or "injurious" MV group (WPM group or WIM group）and PLCE1 knock-down(PLCE1-KD)）rats+ "lung protective" or " injurious" MV group (PPM group or PIM group). Rats were subjected to 2 h "lung protective" tidal volume(TV)=7 mL/kg, positive end expiratory pressure (PEEP)=5 cmH2O) or "injurious" (TV=20 mL/kg, PEEP=0 cmH2O) MV. The expressions of PLCEl and cytoplasmic phospholipase A2(C-PLA2) were examined by Western blotting and real-time quantitative PCR(QPCR). Enzyme-linked immunosorbent assay (ELISA) was used to detect the levels of arachidonic acid (AA) metabolites such as prostacyclin (PGI2), thromboxane A2 (TXA2) and leukotriene B4 (LTB4) in the lung tissue. The pulmonary permeability index and the lung wet/dry weight (W/D) ratio were determined to evaluate the permeability of PMEC (PMVECs). The severities of lung injury were evaluated by pathological morphology scores of lung tissues. 
Results In WIM and PIM groups, PLCE1 and C-PLA2 expressions at both the protein and mRNA levels were significantly upregulated, the levels of PGI2,TXA2 and LTB4 in lungs were increased, and pulmonary permeability index,lung W/D ratio,and pathological morphology scores of lung tissues were significantly increased as compared with those in WPM and PPM groups (P＜0.05). Under the same MV mode, the expression levels of PLCE1 and C-PL2 at both the protein and mRNA levels in rat lung tissue, the levels of PGI2, TXA2, and LTB4 in the lungs, and various indicators for evaluating lung injury were significantly lower in PIM and PPM groups than in WIM and WPM groups (P＜0.05). 
Conclusion Downregulation of PLCE1 can alleviate MV-induced increased PMVEC permeability by inhibiting C-PL2 activity, exerting a protective effect on the lungs, suggesting that PLCE1 may be a potential intervention target for anti-VILI therapy.

Key words: ventilator-induced lung injury, respiration, artificial, endothelial cells