Effect of curcumin pretreatment on JNK signaling pathway during one-lung ventilation-induced acute lung injury in mice

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 table: two-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 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. Key words: Curcumin; JNK mitogen-activated protein kinases; Apoptosis; Respiratory distress syndrome, adult; Respiration, artificial