Effect of curcumin pretreatment on JNK signaling pathway during one-lung ventilation-induced acute lung injury in mice / 中华麻醉学杂志

ABSTRACT

Objective To evaluate the effect of curcumin pretreatment on c-Jun N-terminal kinase (JNK) signaling pathway during one-lung ventilation (OLV)-induced acute lung injury in mice.Methods Ninety SPF male C57BL/6J mice,aged 6-9 weeks,weighing 18-24 g,were randomly divided into 6 groups (n=15 each) using a random number tabletwo-lung ventilation (TLV) group;OLV group;curcumin 100,150,200 and 250 mg/kg groups (C100,C150,C200 and C250 groups).The corresponding doses of curcumin were administered intraperitoneally at 2 h before one-lung ventilation in C100,C150,C200 and C250 groups.The animals were tracheally intubated and mechanically ventilated in volume-controlled mode.The ventilator settings were adjusted to maintain the end-tidal pressure of carbon dioxide at 35-45 mmHg.In OLV,C100,C150,C200 and C250 groups,unilateral lung was ventilated for 1.5 h followed by 0.5 h of TLV.Bilateral lungs were ventilated for 2.0 h in group TLV.Peak airway pressure and airway pressure were recorded at 1.5 h of OLV and 0.5 h of TLV.At the end of mechanical ventilation,left lungs were removed for microscopic examination of the pathologic changes,and the index of quantitative assessment for alveolar damage (IQA) was recorded.Wet/dry lung weight ratio (W/D ratio) was determined,and the cell apoptosis in lung tissues was detected using TUNEL.The apoptosis index (AI) was calculated.The expression of JNK mRNA was determined using real-time polymerase chain reaction.The expression of JNK and phosphorylated JNK was determined by Western blot.The phosphorylation of JNK was calculated.Results Compared with group TLV,the IQA,W/D ratio,AI,expression of JNK mRNA and phosphorylation of JNK were significantly increased in group OLV (P＜0.05).Compared with group OLV,the IQA,W/D ratio,AI,expression ofJNK mRNA and phosphorylation of JNK were significantly decreased in C150,C200 and C250 groups,the parameters mentioned above were significantly decreased in sequence in C100,C150,C200 and C250 groups (P＜0.05),and no significant change was found in the parameters mentioned above in group C100 (P＞ 0.05).Compared with group OLV,the pathological changes were significantly attenuated in sequence in C150,C200 and C250 groups.Conclusion The mechanism by which curcumin pretreatment reduces cell apoptosis during OLV-induced acute lung injury is related to inhibition of JNK signaling pathway activation in mice.