吡咯烷二硫代氨基甲酸对百草枯肺损伤Nrf2激活的影响  

The effects of pyrrolidine dithiocarbamate on the activation of Nrf2 pathway after paraquat inducedlung injury in rats

作　　者：史晶[1] 高渝峰[1] 陈少波[2] 潘启豪[2] 廖晓星[3] 胡春林[3] 

机构地区：[1]广州市第十二人民医院急诊科,广州510620 [2]中山大学中山医学院 [3]中山大学附属第一医院急诊科

出　　处：《中华急诊医学杂志》2012年第12期1337-1341,共5页Chinese Journal of Emergency Medicine

基　　金：广东省医学科研基金项目（2010501）;广州市医药卫生科技项目（2009-YB-111）

摘　　要：目的观察吡咯烷二硫代氨基甲酸（PDTC）对百草枯（PQ）中毒后sD大鼠肺损伤和Nrf2通路激活的影响。方法48只成年雄性sD大鼠建立PQ肺损伤模型后随机（随机数字法）分为对照组（Contrik）和PDTC组。中毒后1、2、3周各处死3只动物取肺组织，HE染色行急性肺损伤（ALI）评分，Masson染色鉴定肺纤维化（LF）程度，组织匀浆测定MDA、GSH含量，Westonblot检测磷酸化Nrf2水平。两样本均数的比较用成组t检验，生存曲线用Wilcoxon（Gehan）检验。结果大鼠中毒后出现了明显的中毒症状，Control组和PDTC组各有4只和9只动物存活到实验结束，PDTC明显延长动物的存活时间，Wilcoxon（Gehan）=10．17023，P=0．001。Control组肺内MDA水平都高于PDTC组，而GSH水平均低于PDTC组，差异有统计学意义。PQ中毒后PDTC组肺内p-Nrf2水高于Control组，1周：（0．32±0．04）vs．（0．23±0．05），P=0．003；2周：（0．62±0．06）vs．（0．33±0．03），P〈0．001；3周：（0．61±0．04）vs．（0．33±0．05），P〈0．001。PDTC组AIL评分低于Control组，ALl分别为1周：（5±0．95）vs．（8±1．23），P=0．002；2周：（9±1．18）vs．（11±1．02），P=0．019；3周：（11±1．33）vs．（12±1．42），P=0．002。Control组动物中毒后1至3周肺纤维化程度分别为（40．87±7．25）％、（43．38±5．71）％和（45．91±3．97）％，明显高于PDTC组的（32．92±2．34）％、（33．45±3．04）％和（35．27±3．81）％，P值分别为0．017、0．001和0．001。结论PDTC减轻PQ中毒后肺损伤、肺纤维化，延长动物的存活时间与激活Nrf2通路及增强抗氧化能力有关。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 Forty- eight 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 （ALl） 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

关 键 词：百草枯 氧化应激 肺损伤 吡咯烷二硫代氨基甲酸 Nrf2通路 

分 类 号：R965[医药卫生—药理学]