核因子-κB抑制剂吡咯烷二硫代氨基甲酸对百草枯中毒后早期肺损伤的影响

Effects of NF-KB inhibitor pyrrolidine dithiocarbamate on the early-stage acute lung injury induced byparaquat

目的观察核因子（NF）-KB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PDTC100mg／kg腹腔内注射，PQ＋PBS组给予PBS腹腔内注射。24、48和72h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（AIL）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—Ot、IL-6含量和免疫印迹法检测肺内NF．KB激活情况。结果与PQ＋PBS组相比，PDTC提高大鼠PQ中毒后的72h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、48h和72h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、48h和72h的肺内髓过氧化物酶（MP0）阳性细胞数、肺组织内TNF-α、IL-6蛋白水平和胞核、胞质NF．KBP65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—KB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。

Objective To determine the effects of pyrrolidine dithiocarbamate （PDTC）, a nuclear factor-KB （NF-KB） 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 group （32 SD rats were treated with phosphate buffer solution） and PQ＋PDTC group （32 SD rats were treated with 100 mg/kg PDTC）. The survival rate of two groups was assessed at hours 24, 48 and 72 respectively. Haematoxylineosin 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-KB in the lungs was assessed by using Western blotting. Results PDTC improved the surviva/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=O.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（ll.5±l.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-KB in the nucleus and cytoplasm （all P〈O.05）. Conclusion PDTC reduces early- stage mortality of acute lung injury by suppressing infiltration of myeloperoxidase-positive inflammatory cells and inhibiting NF-KB activation leading to decreased TNF-α andIL-6 expression in the lungs.