Effect of sevoflurane on unfolded protein response-related cell apoptosis during acute lung injury in rats undergoing cardiopulmonary bypass

Abstract

Objective To evaluate the effect of sevoflurane on unfolded protein response (UPR)-related cell apoptosis during acute lung injury in rats undergoing cardiopulmonary bypass (CPB). Methods Forty-eight clean-grade healthy adult male Sprague-Dawley rats, aged 6-8 weeks, weighing 250-300 g, were allocated into 3 groups (n=16 each) using a random number table method: sham operation group (Sham group), CPB group and sevoflurane group (Sev group). Left common carotid artery and right internal jugular vein were only cannulated in group Sham.After establishing CPB, the flow rate was gradually adjusted to the maximum (100 ml·kg-1·min-1) and maintained for 60 min in group CPB.Two percent sevoflurane was inhaled for 30 min, and 15 min later the model of CPB was established in Sev group.Rats were sacrificed at 1 h after the end of CPB, lungs were removed and lung tissues were obtained.The pathological changes and ultrastructure of lung tissues were examined with a light microscope and with an electron microscope, respectively.The wet to dry weight ratio (W/D ratio), apoptosis in lung cells (by TUNEL assay), expression of glucose-regulated protein 78 (GRP78), CCAAT/enhancer-binding protein homologous protein (CHOP), c-Jun N-terminal kinase (JNK) and caspase-12 mRNA was determined by real-time polymerase chain reaction.The expression of GRP78, CHOP, phosphorylated JNK (p-JNK) and caspase-12 was detected by Western blot.The index of quantitative assessment of histologic lung injury (IQA) was measured, and apoptotic index (AI) was calculated. Results Compared with Sham group, the W/D ratio, IQA and AI were significantly increased, the expression of GRP78, CHOP, JNK and caspase-12 was up-regulated (P<0.05), and the pathological changes of lung tissues were accentuated in CPB group.Compared with CPB group, the W/D ratio, IQA and AI were significantly decreased, the expression of GRP78, CHOP, JNK and caspase-12 was down-regulated (P<0.05), and the pathological changes of lung tissues were significantly attenuated in Sev group. Conclusion The mechanism by which sevoflurane mitigates acute lung injury induced by CPB is related to inhibiting UPR-related cell apoptosis in lung tissues of rats. Key words: Anesthetics, Inhalation; Extracorporeal circulation; Lung injury; Apoptosis