摘要目的 观察核因子(NF)-κB抑制剂吡咯烷二硫代氨基甲酸(PDTC)对百草枯(PQ)中毒后早期肺损伤的影响.方法 64只成年雄性SD大鼠建立PQ肺损伤模型,数字随机法分为PQ+PDTC和PQ+PBS组,每组32只.PQ+PDTC组给予PDTC 100 mg/kg腹腔内注射,PQ+PBS组给予PBS腹腔内注射.24、48和72 h后观察两组动物存活率,应用苏木精-伊红(HE)染色观察急性肺损伤(ALL)情况并评分；免疫组化检测肺组织炎性细胞浸润；ELISA法检测肺组织内TNF-α、IL-6含量和免疫印迹法检测肺内NF-κB激活情况.结果 与PQ+PBS组相比,PDTC提高大鼠PQ中毒后的72 h内存活率[24/32(75％)比13/32(40.6％),P=0.015].PDTC改善大鼠PQ中毒后24、48 h和72 h的肺损伤评分(7.5±1.0比9.8±1.5,9.7±0.8比12.0±0.9,11.5±1.0比14.5±1.0,均P＜0.05).PDTC降低大鼠PQ中毒后24、48 h和72 h的肺内髓过氧化物酶(MPO)阳性细胞数、肺组织内TNF-α、IL-6蛋白水平和胞核、胞质NF-κB P65蛋白浓度(均P＜0.05).结论 PDTC可减少大鼠PQ中毒后早期炎性细胞的浸润并抑制NF-κB的激活,使致炎因子TNF-α、IL-6表达下降,减轻肺损伤,降低早期病死率.

abstractsObjective To determine the effects of pyrrolidine dithiocarbamate(PDTC),a nuclear factor-κB (NF-κB) inhibitor,on paraquat-induced early-stage acute lung injury.Methods Following establishment of paraquat-induced lung injury mice model,64 adult male SD rats were randomly divided into PQ+PBS gioup (32 SD rats were treated with phosphate buffer solution) and PQ+PDTC group (32 SD rats were treatecl with 100 mg/kg PDTC).The survival rate of two groups was assessed at hours 24,48 and 72 respectively.Haematoxylin-eosin staining was employed to assess the acute lung injury for scoring,and immunochemical assay was used to detect inflammatory cell infiltration in the lungs.The level of TNF-α and IL-6 was measured by enzyme-linked immunosorbent assay and activation of NF-κB in the lungs was assessed by using Western blotting.Results PDTC improved the survival rate at 72 hours as compared with group PQ+PBS[24/32(75％) in group PQ+PDTC vs 13/32(40.6%) in group PQ+PBS,P=0.015] and acute lung injury score at 24 hours (7.5±1.0 vs 9.8±1.5),48 hours (9.7±0.8 vs 12.0±0.9) and 72 hours (11.5±1.0 vs 14.5±1.0) (all P＜0.05).PDTC resulted in reduced cell count with myeloperoxidase expression,the levels of TNF-α and IL-6 in the lungs and the protein levels of NF-κB in the nucleus and cytoplasm (all P＜0.05).Conclusion PDTC reduces early-stage mortality of acute lung injury by suppressing infiltration of myeloperoxidase-positive inflammatory cells and inhibiting NF-κB activation leading to decreased TNF-α and IL-6 expression in the lungs.