Effects of curcumin pretreatment on expression of Nrf2 protein during ventilator-induced lung injury in rabbits

Abstract

Objective To evaluate the effects of curcumin pretreatment on the expression of Nrf2 protein during ventilator-induced lung injury in rabbits.Methods Twenty-four healthy male New Zealand white rabbits,aged 3-6 months,weighing 2.5-3.0 kg,were randomized into 3 groups (n =8 each) using a random number table:two-lung ventilation (TLV) group; one-lung ventilation (OLV) group; and curcumin pretreatment group (group Cur).In group Cur,curcumin 40 mg/kg (dissolved in 2 ml of 1％ sodium carboxymethylcellulose) was given via a gastric tube into the stomach twice a day for 7 consecutive days starting from 7 days before ventilation,while the equal volume of sodium carboxymethylcellulose was given via a gastric tube instead of curcumin in TLV and OLV groups.All the rabbits were tracheostomized,and a tracheal tube was inserted to perform TLV in TLV group,and a tracheal tube was inserted into the right bronchus to establish OLV in OLV and Cur groups.Volumecontrolled ventilation was used in the three groups and the ventilatory parameters were regulated to maintain SpO2 ＞ 90 ％.Immediately before beginning of ventilation (T0) and at 1,2 and 3 h of ventilation (T1-3),arterial blood samples were obtained for blood gas analysis and determination of PaO2.The oxygenation index was calculated.At the end of ventilation,the rabbits were sacrificed and right lungs were removed for determination of wet/dry lung weight ratio (W/D ratio).The right lower lobe was isolated and puhmonary specimens were obtained for determination of malondialdehyde (MDA) content and superoxide dismutase (SOD) activity (using colorimetric method) and the expression of Nrf2 and HO-1 protein (by Western blot) in lung tissues and for microscopic examination of pathological changes of the lung which were scored.Results Compared with group TLV,the W/D ratio,pathological scores,MDA content,and expression of Nrf2 and HO-1 were significantly increased,and the SOD activity and oxygenation index at T2,3 were decreased in OLV and Cur groups (P ＜ 0.05).Compared with group OLV,the W/D ratio,pathological scores,and MDA content were significantly decreased,and the SOD activity,oxygenation index at T3,and expression of Nrf2 and HO-1 were increased in group Cur (P ＜ 0.05).Conclusion Curcumin pretreatment reduces ventilator-induced lung injury through promoting the expression of Nrf2 protein in lung tissues in rabbits. Key words: Curcumin ; Respiration, artificial ; Respiratory distress syndrome, adult ; NF-E2-related factor 2