百草枯中毒与AMPK信号通路

doi:10.3969/j.issn.1002-1949.2019.11.020

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摘要百草枯(PQ) 中毒的治疗是一个世界性难题，迄今为止尚无特效解毒药。研究发现，氧化应激、炎症反应及纤维化的形成在PQ 中毒中起重要作用。而腺苷酸活化蛋白激酶（AMPK）作为能量感受器，除调节能量平衡外，通过调节其上下游信号，还具有抗氧化、抗炎及逆转纤维化的作用，因此，该信号通路近年来在PQ中毒和治疗中的作用受到关注。本文将对AMPK信号通路与PQ 中毒的关系作一综述。

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	吴潦章
	周满红

关键词 ：百草枯（PQ）, 腺苷酸活化蛋白激酶（AMPK）, 氧化应激, 炎症反应

基金资助:国家自然科学基金(81460291)；贵州省科学技术基金（黔科合J字［2014］2183号）；贵州省研究生工作站(GZZ2017006)

通讯作者: 周满红（1963-），男，博士，主任医师，E-mail:1067637135@qq.com。

作者简介: 吴潦章（1986-），男，硕士，主治医师，E-mail:286973982@qq.com。

引用本文:

吴潦章，周满红. 百草枯中毒与AMPK信号通路[J]. 中国急救医学, 2019, 39(11): 1105-1110.
Wu Liao-zhang, Zhou Man-hong. Paraquat poisoning and AMPK signaling pathway. Chinese Journal of Critical Care Medicine, 2019, 39(11): 1105-1110.

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http://www.cnemergency.org.cn/CN/10.3969/j.issn.1002-1949.2019.11.020 或 http://www.cnemergency.org.cn/CN/Y2019/V39/I11/1105

［1］Gil HW, Hong JR, Jang SH, et al. Diagnostic and therapeutic approach for acute paraquat intoxication［J］. J Korean Med Sci, 2014, 29(11):1441-1449.  ［2］Wei T, Tian W, Liu F, et al. Protective effects of exogenous beta-hydroxybutyrate on paraquat toxicity in rat kidney［J］. Biochem Biophys Res Commun, 2014, 447(4):666-671.  ［3］Hardie DG. AMP-activated protein kinase: an energy sensor that regulates all aspects of cell function［J］. Genes Dev, 2011, 25(18):1895-1908. ［4］Mihaylova MM, Shaw RJ. The AMPK signalling pathway coordinates cell growth, autophagy and metabolism［J］. Nat Cell Biol, 2011, 13(9):1016-1023.  ［5］Dos Santos CC, Gopal B, Verma S. Metformin: An old dog with a new trick［J］. Cell Metab, 2018, 28(3):334-336.  ［6］Rangarajan S, Bone NB, Zmijewska AA, et al. Metformin reverses established lung fibrosis in a bleomycin model［J］. Nat Med, 2018, 24(8):1121-1127.  ［7］Lin JL, Lin-Tan DT, Chen KH, et al. Repeated pulse of methylprednisolone and cyclophosphamide with continuous dexamethasone therapy for patients with severe paraquat poisoning［J］. Crit Care Med, 2006, 34(2):368-373.  ［8］Dinis-Oliveira RJ, Pontes H, Bastos ML, et al. An effective antidote for paraquat poisonings: the treatment with lysine acetylsalicylate［J］. Toxicology, 2009, 255(3):187-193.  ［9］Sun B， Chen YG. Advances in the mechanism of paraquat-induced pulmonary injury［J］. Eur Rev Med Pharmacol Sci, 2016, 20(8):1597-1602. 〖ZK)〗 ［10］Liu S, Liu K, Sun Q, et al. Consumption of hydrogen water reduces paraquat-induced acute lung injury in rats［J］. J Biomed Biotechnol, 2011, 2011:305 086. ［11］Ishida Y, Takayasu T, Kimura A, et al. Gene expression of cytokines and growth factors in the lungs after paraquat administration in mice［J］. Leg Med (Tokyo), 2006, 8(2):102-109.  ［12］Donnelly TJ, Meade P, Jagels M, et al. Cytokine, complement, and endotoxin profiles associated with the development of the adult respiratory distress syndrome after severe injury［J］. Crit Care Med, 1994, 22(5):768-776.  ［13］El-Tahan RR, Ghoneim AM, El-Mashad N. TNF-α gene polymorphisms and expression［J］. Springerplus, 2016, 5(1):1508.  ［14］Chen CJ, Shi Y, Hearn A, et al. MyD88-dependent IL-1 receptor signaling is essential for gouty inflammation stimulated by monosodium urate crystals［J］. J Clin Invest, 2006, 116(8):2262-2271.  ［15］Ren K, Torres R. Role of interleukin-1beta during pain and inflammation［J］. Brain Res Rev, 2009, 60(1):57-64. ［16］Gabay C. Interleukin-6 and chronic inflammation［J］. Arthritis Res Ther, 2006, 8 (Suppl 2):S3. ［17］Lopez-Rodriguez E, Boden C, Echaide M, et al. Surfactant dysfunction during overexpression of TGF-β1 precedes profibrotic lung remodeling in vivo［J］. Am J Physiol Lung Cell Mol Physiol, 2016, 310(11):L1260-1271. ［18］Chitra P, Saiprasad G, Manikandan R, et al. Berberine attenuates bleomycin induced pulmonary toxicity and fibrosis via suppressing NF-κB dependant TGF-β activation: a biphasic experimental study［J］. Toxicol Lett, 2013, 219(2):178-193.  ［19］Tsai HL, Chang JW, Yang HW, et al. Amelioration of paraquat-induced pulmonary injury by mesenchymal stem cells［J］. Cell Transplant, 2013, 22(9):1667-1681. ［20］Xu L, Xu J, Wang Z. Molecular mechanisms of paraquat-induced acute lung injury: a current review［J］. Drug Chem Toxicol, 2014, 37(2):130-134.  ［21］Liu MW, Su MX, Tang DY, et al. Ligustrazin increases lung cell autophagy and ameliorates paraquat-induced pulmonary fibrosis by inhibiting PI3K/Akt/mTOR and hedgehog signalling via increasing miR-193a expression［J］. BMC Pulm Med, 2019, 19(1):35.  ［22］Niso-Santano M, González-Polo RA, Bravo-San Pedro JM, et al. Activation of apoptosis signal-regulating kinase 1 is a key factor in paraquat-induced cell death: modulation by the Nrf2/Trx axis［J］. Free Radic Biol Med, 2010, 48(10):1370-1381.  ［23］Huang J, Ning N, Zhang W. Effects of paraquat on IL-6 and TNF-alpha in macrophages［J］. Exp Ther Med, 2019, 17(3):1783-1789.  ［24］Hu X, Shen H, Wang Y, et al. Aspirin-triggered resolvin D1 alleviates paraquat-induced acute lung injury in mice［J］. Life Sci, 2019, 218:38-46. ［25］Hong GL, Cai QQ, Tan JP, et al. Mifepristone-inducible recombinant adenovirus attenuates paraquat-induced lung injury in rats［J］. Hum Exp Toxicol, 2015, 34(1):32-43.  ［26］de Oliveira MR, de Bittencourt Brasil F, Fürstenau CR. Inhibition of the Nrf2/HO-1 axis suppresses the mitochondria-relatedprotection promoted by gastrodin in human neuroblastoma cells exposed to paraquat［J］. Mol Neurobiol, 2019, 56(3):2174-2184.  ［27］Daskalopoulos EP, Dufeys C, Bertrand L, et al. AMPK in cardiac fibrosis and repair: Actions beyond metabolic regulation［J］. J Mol Cell Cardiol, 2016, 91:188-200.  ［28］Carling D, Mayer FV, Sanders MJ, et al. AMP-activated protein kinase: nature′s energy sensor［J］. Nat Chem Biol, 2011, 7(8):512-518. ［29］Milan D, Jeon JT, Looft C, et al. A mutation in PRKAG3 associated with excess glycogen content in pig skeletal muscle［J］. Science, 2000, 288(5469):1248-1251.  ［30］Hawley SA, Davison M, Woods A, et al. Characterization of the AMP-activated protein kinase kinase from rat liver and identification of threonine 172 as the major site at which it phosphorylates AMP-activated protein kinase［J］. J Biol Chem, 1996, 271(44):27 879-27 887.  ［31］Stein SC, Woods A, Jones NA, et al. The regulation of AMP-activated protein kinase by phosphorylation［J］. Biochem J, 2000, 345 (Pt 3):437-443.  ［32］Wong KA, Lodish HF. A revised model for AMP-activated protein kinase structure: The alpha-subunit binds to both the beta- and gamma-subunits although there is no direct binding between the beta- and gamma-subunits［J］. J Biol Chem, 2006, 281(47):36 434-36 442.  ［33］Polekhina G, Gupta A, Michell BJ, et al. AMPK beta subunit targets metabolic stress sensing to glycogen［J］. Curr Biol, 2003, 13(10):867-871.  ［34］Ewart MA, Kennedy S. AMPK and vasculoprotection［J］. Pharmacol Ther, 2011, 131(2):242-253. ［35］Carling D. AMPK signalling in health and disease［J］. Curr Opin Cell Biol, 2017, 45:31-37.  ［36］Hardie DG. AMPK--sensing energy while talking to other signaling pathways［J］. Cell Metab, 2014, 20(6):939-952.  ［37］Hawley SA, Fullerton MD, Ross FA, et al. The ancient drug salicylate directly activates AMP-activated protein kinase［J］. Science, 2012, 336(6083):918-922.  ［38］Gadalla AE, Pearson T, Currie AJ, et al. AICA riboside both activates AMP-activated protein kinase and competes with adenosine for the nucleoside transporter in the CA1 region of the rat hippocampus［J］. J Neurochem, 2004, 88(5):1272-1282.  ［39］Cool B, Zinker B, Chiou W, et al. Identification and characterization of a small molecule AMPK activator that treats key components of type 2 diabetes and the metabolic syndrome［J］. Cell Metab, 2006, 3(6):403-416.  ［40］许延龙,武坷鑫,王前,等. AMPK-mTOK信号通路参与百草枯致PC12细胞的自噬抑制作用［J］. 中华劳动卫生职业病杂志, 2018, 36(11):801-807.  ［41］Tohyama D, Yamaguchi A. A critical role of SNF1A/dAMPKalpha (Drosophila AMP-activated protein kinase alpha) in muscle on longevity and stress resistance in Drosophila melanogaster［J］. Biochem Biophys Res Commun, 2010, 394(1):112-118. ［42］Liu SJ, Yin CX, Ding MC, et al. Berberine inhibits tumor necrosis factor-α-induced expression of inflammatory molecules and activation of nuclear factor-κB via the activation of AMPK in vascular endothelial cells［J］. Mol Med Rep, 2015, 12(4):5580-5586. ［43］Li W, Qiu X, Jiang H, et al. Ulinastatin inhibits the inflammation of LPS-induced acute lung injury in mice via regulation of AMPK/NF-κB pathway［J］. Int Immunopharmacol, 2015, 29(2):560-567. ［44］Park CS, Bang BR, Kwon HS, et al. Metformin reduces airway inflammation and remodeling via activation of AMP-activated protein kinase［J］. Biochem Pharmacol, 2012, 84(12):1660-1670.  ［45］Maniar K, Singh V, Moideen A, et al. Inhalational supplementation of metformin butyrate: A strategy for prevention and cure of various pulmonary disorders［J］. Biomed Pharmacother, 2018, 107:495-506. ［46］Gamad N, Malik S, Suchal K, et al. Metformin alleviates bleomycin-induced pulmonary fibrosis in rats: Pharmacological effects and molecular mechanisms［J］. Biomed Pharmacother, 2018, 97:1544-1553. ［47］Chen X, Walther FJ, Sengers RM, et al. Metformin attenuates hyperoxia-induced lung injury in neonatal rats by reducing the inflammatory response［J］. Am J Physiol Lung Cell Mol Physiol, 2015, 309(3):L262-270. ［48］Jiang C, Zhong R, Zhang J, et al. Reduning injection ameliorates paraquat-induced acute lung injury by regulating AMPK/MAPK/NF-kappaB signaling［J］. J Cell Biochem, 2019, 120(8):12 713-12 723.  ［49］Hu M, Liu B. Resveratrol via activation of LKB1-AMPK signaling suppresses oxidative stress to prevent endothelial dysfunction in diabetic mice［J］. Clin Exp Hypertens, 2016, 38(4):381-387. ［50］Gallo A, Ceolotto G, Pinton P, et al. Metformin prevents glucose-induced protein kinase C-beta2 activation in human umbilical vein endothelial cells through an antioxidant mechanism［J］. Diabetes, 2005, 54(4):1123-1131.  ［51］Wang S, Dale GL, Song P, et al. AMPKalpha1 deletion shortens erythrocyte life span in mice: role of oxidative stress［J］. J Biol Chem, 2010, 285(26):19 976-19 985. ［52］Wang S, Zhang M, Liang B, et al. AMPKalpha2 deletion causes aberrant expression and activation of NAD(P)H oxidase and consequent endothelial dysfunction in vivo: role of 26S proteasomes［J］. Circ Res, 2010, 106(6):1117-1128.  ［53］Hwang AB, Ryu EA, Artan M, et al. Feedback regulation via AMPK and HIF-1 mediates ROS-dependent longevity in caenorhabditis elegans［J］. Proc Natl Acad Sci U S A, 2014, 111(42):E4458-4467. ［54］Meng J, Lv Z, Qiao X, et al. The decay of redox-stress response capacity is a substantive characteristic of aging: Revising the redox theory of aging［J］. Redox Biol, 2017, 11:365-374. ［55］Gamad N, Malik S, Suchal K, et al. Metformin alleviates bleomycin-induced pulmonary fibrosis in rats: Pharmacological effects and molecular mechanisms［J］. Biomed Pharmacother, 2018, 97:1544-1553. ［56］Zhang CX, Pan SN, Meng RS, et al. Metformin attenuates ventricular hypertrophy by activating the AMP-activated protein kinase-endothelial nitric oxide synthase pathway in rats［J］. Clin Exp Pharmacol Physiol, 2011, 38(1):55-62. ［57］Hu L, Su L, Dong Z, et al. AMPK agonist AICAR ameliorates portal hypertension and liver cirrhosis via no pathway in the BDL rat model［J］. J Mol Med (Berl), 2019, 97(3):423-434.  ［58］Yao L, Li J, Li L, et al. Coreopsis tinctoria nutt ameliorates high glucose-induced renal fibrosis and inflammation via the TGF-β1/SMADS/AMPK/NF-κB pathways［J］. BMC Complement Altern Med, 2019, 19(1):14. ［59］Takata T, Motoo Y, Tomosugi N. Effect of saikokeishito, a kampo medicine, on hydrogen peroxide-induced premature senescence of normal human dermal fibroblasts［J］. J Integr Med, 2014, 12(6):495-503.  ［60］Mihaylova MM, Shaw RJ. The AMPK signalling pathway coordinates cell growth, autophagy and metabolism［J］. Nat Cell Biol, 2011, 13(9):1016-1023.  ［61］Blanco-Ayala T, Andérica-Romero AC, Pedraza-Chaverri J. New insights into antioxidant strategies against paraquat toxicity［J］. Free Radic Res, 2014, 48(6):623-640.  ［62］Wen C, Lin F, Huang B, et al. Metabolomics analysis in acute paraquat poisoning patients based on UPLC-Q-TOF-MS and machine learning approach［J］. Chem Res Toxicol, 2019, 32(4):629-637. ［63］Anandhan A, Lei S, Levytskyy R, et al. Glucose metabolism and AMPK signaling regulate dopaminergic cell death induced by gene (alpha-synuclein)-environment (paraquat) interactions［J］. Mol Neurobiol, 2017, 54(5):3825-3842. ［64］Fazakerley DJ, Minard AY, Krycer JR, et al. Mitochondrial oxidative stress causes insulin resistance without disrupting oxidative phosphorylation［J］. J Biol Chem, 2018, 293(19):7315-7328.  ［65］Anandhan A, Lei S, Levytskyy R, et al. Glucose metabolism and AMPK signaling regulate dopaminergic cell death induced by gene (alpha-synuclein)-environment (paraquat) interactions［J］. Mol Neurobiol, 2017, 54(5):3825-3842. ［66］He Y, Zou L, Zhou Y, et al. Adiponectin ameliorates the apoptotic effects of paraquat on alveolar type cells via improvements in mitochondrial function［J］. Mol Med Rep, 2016, 14(1):746-752.  ［67］Powers R, Lei S, Anandhan A, et al. Metabolic investigations of the molecular mechanisms associated with parkinson′s disease［J］. Metabolites, 2017, 7(2): E22.