中华急诊医学杂志
中華急診醫學雜誌
중화급진의학잡지
CHINESE JOURNAL OF EMERGENCY MEDICINE
2012年
12期
1337-1341
,共5页
史晶%高渝峰%陈少波%潘启豪%廖晓星%胡春林
史晶%高渝峰%陳少波%潘啟豪%廖曉星%鬍春林
사정%고투봉%진소파%반계호%료효성%호춘림
百草枯%氧化应激%肺损伤%吡咯烷二硫代氨基甲酸%Nrf2通路
百草枯%氧化應激%肺損傷%吡咯烷二硫代氨基甲痠%Nrf2通路
백초고%양화응격%폐손상%필각완이류대안기갑산%Nrf2통로
Paraquat%Oxidative stress%Acute lung injury%Pyrrolidine dithiocarbamate%Nrf2 pathway
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(Control)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,Weston blot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,ALI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.
目的 觀察吡咯烷二硫代氨基甲痠(PDTC)對百草枯(PQ)中毒後SD大鼠肺損傷和Nrf2通路激活的影響.方法 48隻成年雄性SD大鼠建立PQ肺損傷模型後隨機(隨機數字法)分為對照組(Control)和PDTC組.中毒後1、2、3週各處死3隻動物取肺組織,HE染色行急性肺損傷(ALI)評分,Masson染色鑒定肺纖維化(LF)程度,組織勻漿測定MDA、GSH含量,Weston blot檢測燐痠化Nrf2水平.兩樣本均數的比較用成組t檢驗,生存麯線用Wilcoxon (Gehan)檢驗.結果 大鼠中毒後齣現瞭明顯的中毒癥狀,Control組和PDTC組各有4隻和9隻動物存活到實驗結束,PDTC明顯延長動物的存活時間,Wilcoxon (Gehan)=10.17023,P=0.001.Control組肺內MDA水平都高于PDTC組,而GSH水平均低于PDTC組,差異有統計學意義.PQ中毒後PDTC組肺內p-Nrf2水高于Control組,1週:(0.32±0.04) vs.(0.23±0.05),P=0.003;2週:(0.62±0.06) vs.(0.33±0.03),P<0.001;3週:(0.61±0.04) vs.(0.33±0.05),P<0.001.PDTC組AIL評分低于Control組,ALI分彆為1週:(5±0.95) vs.(8±1.23),P=0.002;2週:(9±1.18) vs.(11±1.02),P=0.019;3週:(11±1.33) vs.(12±1.42),P=0.002.Control組動物中毒後1至3週肺纖維化程度分彆為(40.87±7.25)%、(43.38±5.71)%和(45.91±3.97)%,明顯高于PDTC組的(32.92±2.34)%、(33.45±3.04)%和(35.27±3.81)%,P值分彆為0.017、0.001和0.001.結論 PDTC減輕PQ中毒後肺損傷、肺纖維化,延長動物的存活時間與激活Nrf2通路及增彊抗氧化能力有關.
목적 관찰필각완이류대안기갑산(PDTC)대백초고(PQ)중독후SD대서폐손상화Nrf2통로격활적영향.방법 48지성년웅성SD대서건립PQ폐손상모형후수궤(수궤수자법)분위대조조(Control)화PDTC조.중독후1、2、3주각처사3지동물취폐조직,HE염색행급성폐손상(ALI)평분,Masson염색감정폐섬유화(LF)정도,조직균장측정MDA、GSH함량,Weston blot검측린산화Nrf2수평.량양본균수적비교용성조t검험,생존곡선용Wilcoxon (Gehan)검험.결과 대서중독후출현료명현적중독증상,Control조화PDTC조각유4지화9지동물존활도실험결속,PDTC명현연장동물적존활시간,Wilcoxon (Gehan)=10.17023,P=0.001.Control조폐내MDA수평도고우PDTC조,이GSH수평균저우PDTC조,차이유통계학의의.PQ중독후PDTC조폐내p-Nrf2수고우Control조,1주:(0.32±0.04) vs.(0.23±0.05),P=0.003;2주:(0.62±0.06) vs.(0.33±0.03),P<0.001;3주:(0.61±0.04) vs.(0.33±0.05),P<0.001.PDTC조AIL평분저우Control조,ALI분별위1주:(5±0.95) vs.(8±1.23),P=0.002;2주:(9±1.18) vs.(11±1.02),P=0.019;3주:(11±1.33) vs.(12±1.42),P=0.002.Control조동물중독후1지3주폐섬유화정도분별위(40.87±7.25)%、(43.38±5.71)%화(45.91±3.97)%,명현고우PDTC조적(32.92±2.34)%、(33.45±3.04)%화(35.27±3.81)%,P치분별위0.017、0.001화0.001.결론 PDTC감경PQ중독후폐손상、폐섬유화,연장동물적존활시간여격활Nrf2통로급증강항양화능력유관.
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.