The effects of pyrrolidine dithiocarbamate on the activation of Nrf2 pathway after paraquat induced lung injury in rats / 中华急诊医学杂志

ABSTRACT

Objective To explore the effects of pyrrolidine dithiocarbamate (PDTC) on the acute lung injury and the activation of Nrf2 pathway after Paraquat (PQ) induced lung injury.Methods Fortyeight adult male SD rats with lung injury induced by PQ were randomly (random number) divided into control group and PDTC group.Three animals were sacrificed at every 1-week interval,7d,14d and 21 days after PQ intoxication,and the lungs of rats were removed for acute lung injury score after HE staining,and for lung fibrosis assessment after Masson staining,and the levels of reduced glutathione (GSH) and malondialdehyde (MDA) in the lung tissue homogenate were assayed and the phosphorylation of Nrf2 (nuclear-E2-related factor 2) was detected by Weston blot.The mean values of detected variables between two groups were compared by t test,and survival curve was tested by Wilcoxon (Gehan) test.Results The intoxication symptoms of rats were obvious,and 4 rats in control group and 9 rats in PDTC group survived until 21days.The survival time of animals in PDTC group was longer than that in control group (Wilcoxon (Gehan) =10.17023,P =0.001).The levels of MDA in control group were higher than those in PDTC group,while the levels of GSH in control group were lower than those in PDTC group.The levels of phosphorylation of Nrf2 in PDTC group were higher than those in control group at 1-week intervals,1-week(0.32±0.04) vs.(0.23±0.05),P=0.003; 2-week(0.62±0.06) vs.(0.33±0.03),P＜0.001; 3-week(0.61 ±0.04) vs.(0.33±0.05),P＜0.001.The acute lung injury (ALI) scores in PDTC group were lower than those in control group,1-week(5 ± 0.95) vs.(8 ± 1.23),P =0.002 ; 2-week(9±1.18) vs.(11±1.02),P=0.019; 3-week(11±1.33) vs.(12±1.42),P=0.002.The percentages of lung fibrosis at 1-week intervals after PQ intoxication were (40.87 ± 7.25) ％,(43.38 ±5.71)％ and (45.91 ± 3.97)％ in control group,and they were higher than those in PDTC group (32.92±2.34)％,(33.45 ±3.04)％ and (35.27 ±3.81)％ in PDTC group,P=0.017,0.001 and 0.001 respectively.Conclusions Attenuation of acute lung injury and lung fibrosis,and prolongation of survival time of SD rats by PDTC were associated with activation of Nrf2 pathway.