Pretreatment with Erythropoietin Attenuates Lung Ischemia/Reperfusion Injury via Toll-Like Receptor-4/Nuclear Factor-κB (TLR4/NF-κB) Pathway

BACKGROUND Lung ischemia/reperfusion injury (LIRI) is a medical problem featuring pulmonary dysfunction and damage. The present study aimed to investigate the protective effects of erythropoietin (EPO), which has been reported to be an anti-inflammatory agent, on LIRI through inhibiting the TLR-4/NF-κB signaling pathway. MATERIAL AND METHODS All rats were randomly divided into 3 groups (n=8): a control group, a vehicle+LIRI group, and an EPO+LIRI group. LIRI included 90-min ischemia and 120-min reperfusion, while RhEpo was administered (3 kU/kg) intraperitoneally 2 h before the operation. Levels of pulmonary inflammatory responses were examined by analyzing pulmonary permeability index (PPI), oxygenation index, histology, and expressions of inflammatory cytokines. RESULTS Pretreatment with EPO significantly decreased lung W/D ratio, BALF leukocytes count and percentage, and PPI but increased oxygenation index compared with the LIRI group (P<0.05). More importantly, with EPO pretreatment there was less pathological damage compared with the vehicle group. Expressions of inflammatory cytokines (TNF-α, IL-6, and IL-1β) in the serum were significantly lower in the EPO group than in the LIRI group (P<0.05). In addition, gene expression and protein expression of TLR-4 and NF-κB were significantly inhibited with EPO pretreatment compared with the LIRI group (P<0.05). CONCLUSIONS Our study id the first to report that EPO protects lung injuries after LIRI through inhibiting the TLR4-NF-κB signaling pathway, which provides solid evidence for the use of EPO as a therapeutic agent for treating LIRI in the future.