急性百草枯中毒肺损伤机制和临床治疗研究进展
摘要
百草枯(PQ),化学名称是1-1-二甲基-4-4-联吡啶阳离子盐,是一种快速灭生性除草剂,其对人畜具有很强毒性,且无特效解毒药。百草枯可经消化道、皮肤和呼吸道吸收,临床致死病例主要为自服或误服,起病凶险,病情变化迅速,它是目前致死性最高的农药中毒事件。百草枯急性中毒后进入人体可使肺、肾、肝、脑等多器官出现损伤,但其中肺是主要的靶器官,在肺组织中的浓度最高,是血浆浓度的10～90倍,早期表现为急性肺损伤(ALI)或急性呼吸窘迫综合征(ARDS),后期则发展为肺泡内和肺间质纤维化,成为患者死亡的主要原因。
引文
[1]陈俊平.百草枯中毒致肺纤维化的急救措施[J].世界最新医学信息文摘,2017,17(1):81-81.
[2] Cao Y,Li J,Ou Z,et al.Inhibition of pulmonary nuclear factor-KappaB and tumor necrosis factor-alpha ex-pression by diallyl sulfide in rats with paraquat poi-soning[J].Zhonghua Wei Zhong Bing Ji Jiu Yixue,2015,27(4):274-279.
[3]聂时南,黄昌保.百草枯中毒诊治:现状与前景[J].临床急诊杂志,2016,17(5):329-332.
[4]孙昊,张劲松,康健,等.不同时段剂量腹腔注射百草枯致小鼠肺损伤及肺纤维化效果评价[J].中华急诊医学杂志,2016,25(11):1386-1392.
[5]裴学勇,李倩.百草枯中毒致肺纤维化机制及临床治疗研究进展[J].中国实用医刊,2016,43(12):116-119.
[6]李雪飞,张天杰.百草枯诱导大鼠肺纤维化的机制分析[J].湘南学院学报,2015,17(4):4-7.
[7] Shao X,Chen JH.Progress on pathogenesis and treatment of paraquat-induced pulmonary fibrosis[J].J Zhejiang Uni Med sci,2014,43(6):717-727.
[8] Xu L,Xu J,Wang Z.Molecular mechanisms of paraquatinducedacutelung injury:a current review[J].Drug Chemical Toxicol,2014,37(2):130-134.
[9] Zhang N,Xie YP,Pang L,et al.Paraquat increases connectivetissue growth factor expression andimpairs lung fibroblast proliferation and viscoelasticity[J].Hum Exp Toxicol,2014,33(12):1232-1240.
[10] Gil HW,Hong JR,Jang SH,et al.Diagnostic and therapeutic approachfor acute paraquat intoxication[J].J Korean Med sci,2014,29(11):1441-1449.
[11]赵春燕,刘畅,朱忠立,等.百草枯通过调节Wnt/β-catenin信号通路促进肺泡上皮细胞上皮间质转化[J].局解手术学杂志,2017,26(11):790-795.
[12]马柳梅.不同血液净化方法对百草枯中毒患者血清TNF-α及IL-10的影响[D].河北医科大学,2014.
[13]胡峰,张贺,祝巍,等.百草枯中毒患者肾脏损害的病理形态学表现(附8例报告)[A].全军肾脏病学专业委员会暨牡丹江市肾脏病学分会学术年会[C],2014.
[14]赵祥宇.百草枯中毒救治药物与措施的探索性研究[D].中国人民解放军军事医学科学院,2016.
[15] Qian J,Ye Y,Lv L,et al.FTY720attenuates paraquat-induced lung injury in mice[J].Int Immunopharmacol,2014,21(2):426-431.
[16] Shimada H,Harai K,Simamura E,et al.Paraquat toxicity induced by voltagedependent anion channel 1acts as an NADH-dependent oxidorectase[J].J Biol Chem,2009,284(42):28642-28649.
[17] Dinis-Oliveira RJ,Dualte J,Sanchez-Navarro A,et al.Paraquat poisonings:mechanisms of lung toxicity,clinical features,and treatment[J].Criti Revi Tox,2008,38(1):13-71.
[18] Roberts DM,Wilks MF,Roberts MS,et al.Changes in the concentrations of creatinine,cystatin C and NGAL in patients with acute paraquat self-poisoning[J].Toxicology Letters,2011,202(1):69-74.
[19] Mukhopadhyay P,Rajesh M,Yoshihiro K,et al.Simple quantitative detection of mitochondrial superoxide production in live cells[J].Biochem Biophys Res Commun,2007,358(1):203-208.
[20]田金飞.NF-κB在急性百草枯中毒中的表达及意义[J].医学综述,2011,17(7):985-987.
[21]孟潇潇,刘刊,谈玖婷,等.百草枯中毒大鼠肺纤维化与内质网应激的关系[J].中华危重病急救医学,2013,25(6):331-334.
[22] Cao H,Zhou X,Zhang J,et al.Hydrogensulfide protects against bleomycin induced pulmonary fibrosis in rats by inhibiting NF-kB expression and regulating Thl/Th2balance[J].Toxicol Lett,2014,224(3):387-394.
[23]宋宏伟,刘晓伟,刘志,等.急性百草枯中毒致肺损伤的细胞免疫机制研究进展[A].中国中毒救治首都论坛暨全国中毒及危重症救治学术会议[C],2016.
[24]王小闯,高欣,古长维,等.大鼠百草枯中毒肺内炎症因子表达[J].陕西医学杂志,2012,41(9):1107-1108.
[25]李冬,徐丽艳,常子娟,等.沙利度胺对百草枯诱导小鼠急性肺损伤的干预[J].中华劳动卫生职业病杂志,2013,31(3):178-183.
[26] Wang X,Luo F,Zhao H.Paraquat-induced reactive oxygen species inhibit neutrophil apoptosis via a p38MAPK/NF-kappaB-IL-6/TNF-alpha positive-feedbackcircuit[J].PLoS One,2014,9(4):e93837.
[27] Lopez-Rodriguez E,Boden C,Echaide M,et al.Surfactant dysfunction during overexpression ofTGF-β1precedes profibrotic lung remodeling in vivo[J].Am J Physiol Lung Cell Mol Physiol,2016,310(11):1260-1271.
[28] Chitra P,Saiprasad G,Manikandan R,et al.Berberin eattenuates bleomycin induced pulmonary toxicity an fibrosis via suppressing NF-kB dependant TGF-B activation:a biphasic experimental study[J].Toxicol Lett,2013,219(2):178-193.
[29] Roach KM,Feghali-Bostwick CA,Amrani Y,et al.Lipoxin A4attenuates constitutive and TGF-β1-dependent profibrotic activity in human lung myofibroblasts[J].J Immunol,2015,195(6):2852-2860.
[30] Li G,Yuzhen L,Yi C,et al.DNaseI protectsagainst paraquat-Induced acute lungInjuryand pulmonary fibrosis mediatedby mitochondrialDNA[J].Biomed Res Int,2015,2015:386952.
[31]白雪,盛英杰,戢新平,等.百草枯对肺组织细胞凋亡的影响[J].医学综述,2014,20(1):90-92.
[32] Ran M,Wang YM,Zhao J,et al.Metallothionoins attenuate paraquat-induced acute lung injury in mice through the mechanisms of anti-oxidation and anti-apoptosis[J].Food Chem Toxicol,2014,73(1):140-147.
[33] Li GQ,Li YM,Wei LQ,et al.Comparison between kidney and continuous plasma perfusion for paraquat elimination[J].Am J Med Sci,2014,348(3):195-203.
[34]姜家瑚,柳玉华,褚海涛,等.3种吸附剂对百草枯吸附能力的对比观察[J].检验医学与临床,2011,8(14):1718-1719.
[35] Jones AL,Elton R,Flanagan R.Multiple logistic regression analysis of plasma paraquat concentration as a predictor of outcome in 375cases of paraquat poisoning[J].QJM,1999,92(10):573-578.
[36]刘明伟,苏美仙,秦兰芳,等.阿托伐他汀对百草枯中毒大鼠肺纤维化的影响及机制研究[J].免疫学杂志,2012,28(10):862-866.
[37]] Chang JB,Lin CC,Chiou JF,et al.Treatment of acute paraquat intoxication using recommended megadose of vitamin C:A reappraisal[J].Free Radic Res,2013,24(12):243-256.
[38] Wu WP,Lai MN,Lin CH,et al.Addition of immunosuppressive treatment to hemoperfusion is associated with improved survival after paraquat poisoning:a nationwide study[J].PLoS One,2014,9(1):e87568.
[39]李晓莉,龚媛,张浩,等.环磷酰胺对百草枯中毒致急性肺损伤的疗效及安全性分析[J].中国全科医学,2013,16(9B):3124-3125.
[40] Awadalla EA.Efficacy of vitamin C against liver and kidney damage induced by paraquat toxicity[J].Exp Toxicol Pathol,2012,64(5):431-434.
[41] Tsai HL,Chang JW,Yang HW,et al.Amelioration of paraquat-inducded pulmonaryinjury by mesenchymal stem cells[J].Cell Transplant,2013,22(9):1667-1681.
[42]许黎忠,黄朝忠,戴木森,等.阻断肾素血管紧张素醛固酮系统不同位点对百草枯中毒大鼠肺纤维化的影响[J].福建医学杂志,2013,35(3):65-68.
[43]李海龙,吴守振,李洺,等.红景天苷对百草枯诱发PC12细胞损伤的保护作用[J].陕西中医,2015,34(7):925-928.
[44]菅向东,张华,隋宏,等.百草枯中毒救治“齐鲁方案”(2014)[J].中国工业医学杂志,2014,27(2):119-121.
[45] Vadivelan M,Chellappan A,Suryanarayana BS.The“golden hour”in paraquat poisoning[J].Toxicol Int,2014,21(3):339-340.
[2] Cao Y,Li J,Ou Z,et al.Inhibition of pulmonary nuclear factor-KappaB and tumor necrosis factor-alpha ex-pression by diallyl sulfide in rats with paraquat poi-soning[J].Zhonghua Wei Zhong Bing Ji Jiu Yixue,2015,27(4):274-279.
[3]聂时南,黄昌保.百草枯中毒诊治:现状与前景[J].临床急诊杂志,2016,17(5):329-332.
[4]孙昊,张劲松,康健,等.不同时段剂量腹腔注射百草枯致小鼠肺损伤及肺纤维化效果评价[J].中华急诊医学杂志,2016,25(11):1386-1392.
[5]裴学勇,李倩.百草枯中毒致肺纤维化机制及临床治疗研究进展[J].中国实用医刊,2016,43(12):116-119.
[6]李雪飞,张天杰.百草枯诱导大鼠肺纤维化的机制分析[J].湘南学院学报,2015,17(4):4-7.
[7] Shao X,Chen JH.Progress on pathogenesis and treatment of paraquat-induced pulmonary fibrosis[J].J Zhejiang Uni Med sci,2014,43(6):717-727.
[8] Xu L,Xu J,Wang Z.Molecular mechanisms of paraquatinducedacutelung injury:a current review[J].Drug Chemical Toxicol,2014,37(2):130-134.
[9] Zhang N,Xie YP,Pang L,et al.Paraquat increases connectivetissue growth factor expression andimpairs lung fibroblast proliferation and viscoelasticity[J].Hum Exp Toxicol,2014,33(12):1232-1240.
[10] Gil HW,Hong JR,Jang SH,et al.Diagnostic and therapeutic approachfor acute paraquat intoxication[J].J Korean Med sci,2014,29(11):1441-1449.
[11]赵春燕,刘畅,朱忠立,等.百草枯通过调节Wnt/β-catenin信号通路促进肺泡上皮细胞上皮间质转化[J].局解手术学杂志,2017,26(11):790-795.
[12]马柳梅.不同血液净化方法对百草枯中毒患者血清TNF-α及IL-10的影响[D].河北医科大学,2014.
[13]胡峰,张贺,祝巍,等.百草枯中毒患者肾脏损害的病理形态学表现(附8例报告)[A].全军肾脏病学专业委员会暨牡丹江市肾脏病学分会学术年会[C],2014.
[14]赵祥宇.百草枯中毒救治药物与措施的探索性研究[D].中国人民解放军军事医学科学院,2016.
[15] Qian J,Ye Y,Lv L,et al.FTY720attenuates paraquat-induced lung injury in mice[J].Int Immunopharmacol,2014,21(2):426-431.
[16] Shimada H,Harai K,Simamura E,et al.Paraquat toxicity induced by voltagedependent anion channel 1acts as an NADH-dependent oxidorectase[J].J Biol Chem,2009,284(42):28642-28649.
[17] Dinis-Oliveira RJ,Dualte J,Sanchez-Navarro A,et al.Paraquat poisonings:mechanisms of lung toxicity,clinical features,and treatment[J].Criti Revi Tox,2008,38(1):13-71.
[18] Roberts DM,Wilks MF,Roberts MS,et al.Changes in the concentrations of creatinine,cystatin C and NGAL in patients with acute paraquat self-poisoning[J].Toxicology Letters,2011,202(1):69-74.
[19] Mukhopadhyay P,Rajesh M,Yoshihiro K,et al.Simple quantitative detection of mitochondrial superoxide production in live cells[J].Biochem Biophys Res Commun,2007,358(1):203-208.
[20]田金飞.NF-κB在急性百草枯中毒中的表达及意义[J].医学综述,2011,17(7):985-987.
[21]孟潇潇,刘刊,谈玖婷,等.百草枯中毒大鼠肺纤维化与内质网应激的关系[J].中华危重病急救医学,2013,25(6):331-334.
[22] Cao H,Zhou X,Zhang J,et al.Hydrogensulfide protects against bleomycin induced pulmonary fibrosis in rats by inhibiting NF-kB expression and regulating Thl/Th2balance[J].Toxicol Lett,2014,224(3):387-394.
[23]宋宏伟,刘晓伟,刘志,等.急性百草枯中毒致肺损伤的细胞免疫机制研究进展[A].中国中毒救治首都论坛暨全国中毒及危重症救治学术会议[C],2016.
[24]王小闯,高欣,古长维,等.大鼠百草枯中毒肺内炎症因子表达[J].陕西医学杂志,2012,41(9):1107-1108.
[25]李冬,徐丽艳,常子娟,等.沙利度胺对百草枯诱导小鼠急性肺损伤的干预[J].中华劳动卫生职业病杂志,2013,31(3):178-183.
[26] Wang X,Luo F,Zhao H.Paraquat-induced reactive oxygen species inhibit neutrophil apoptosis via a p38MAPK/NF-kappaB-IL-6/TNF-alpha positive-feedbackcircuit[J].PLoS One,2014,9(4):e93837.
[27] Lopez-Rodriguez E,Boden C,Echaide M,et al.Surfactant dysfunction during overexpression ofTGF-β1precedes profibrotic lung remodeling in vivo[J].Am J Physiol Lung Cell Mol Physiol,2016,310(11):1260-1271.
[28] Chitra P,Saiprasad G,Manikandan R,et al.Berberin eattenuates bleomycin induced pulmonary toxicity an fibrosis via suppressing NF-kB dependant TGF-B activation:a biphasic experimental study[J].Toxicol Lett,2013,219(2):178-193.
[29] Roach KM,Feghali-Bostwick CA,Amrani Y,et al.Lipoxin A4attenuates constitutive and TGF-β1-dependent profibrotic activity in human lung myofibroblasts[J].J Immunol,2015,195(6):2852-2860.
[30] Li G,Yuzhen L,Yi C,et al.DNaseI protectsagainst paraquat-Induced acute lungInjuryand pulmonary fibrosis mediatedby mitochondrialDNA[J].Biomed Res Int,2015,2015:386952.
[31]白雪,盛英杰,戢新平,等.百草枯对肺组织细胞凋亡的影响[J].医学综述,2014,20(1):90-92.
[32] Ran M,Wang YM,Zhao J,et al.Metallothionoins attenuate paraquat-induced acute lung injury in mice through the mechanisms of anti-oxidation and anti-apoptosis[J].Food Chem Toxicol,2014,73(1):140-147.
[33] Li GQ,Li YM,Wei LQ,et al.Comparison between kidney and continuous plasma perfusion for paraquat elimination[J].Am J Med Sci,2014,348(3):195-203.
[34]姜家瑚,柳玉华,褚海涛,等.3种吸附剂对百草枯吸附能力的对比观察[J].检验医学与临床,2011,8(14):1718-1719.
[35] Jones AL,Elton R,Flanagan R.Multiple logistic regression analysis of plasma paraquat concentration as a predictor of outcome in 375cases of paraquat poisoning[J].QJM,1999,92(10):573-578.
[36]刘明伟,苏美仙,秦兰芳,等.阿托伐他汀对百草枯中毒大鼠肺纤维化的影响及机制研究[J].免疫学杂志,2012,28(10):862-866.
[37]] Chang JB,Lin CC,Chiou JF,et al.Treatment of acute paraquat intoxication using recommended megadose of vitamin C:A reappraisal[J].Free Radic Res,2013,24(12):243-256.
[38] Wu WP,Lai MN,Lin CH,et al.Addition of immunosuppressive treatment to hemoperfusion is associated with improved survival after paraquat poisoning:a nationwide study[J].PLoS One,2014,9(1):e87568.
[39]李晓莉,龚媛,张浩,等.环磷酰胺对百草枯中毒致急性肺损伤的疗效及安全性分析[J].中国全科医学,2013,16(9B):3124-3125.
[40] Awadalla EA.Efficacy of vitamin C against liver and kidney damage induced by paraquat toxicity[J].Exp Toxicol Pathol,2012,64(5):431-434.
[41] Tsai HL,Chang JW,Yang HW,et al.Amelioration of paraquat-inducded pulmonaryinjury by mesenchymal stem cells[J].Cell Transplant,2013,22(9):1667-1681.
[42]许黎忠,黄朝忠,戴木森,等.阻断肾素血管紧张素醛固酮系统不同位点对百草枯中毒大鼠肺纤维化的影响[J].福建医学杂志,2013,35(3):65-68.
[43]李海龙,吴守振,李洺,等.红景天苷对百草枯诱发PC12细胞损伤的保护作用[J].陕西中医,2015,34(7):925-928.
[44]菅向东,张华,隋宏,等.百草枯中毒救治“齐鲁方案”(2014)[J].中国工业医学杂志,2014,27(2):119-121.
[45] Vadivelan M,Chellappan A,Suryanarayana BS.The“golden hour”in paraquat poisoning[J].Toxicol Int,2014,21(3):339-340.