肺泡内液体清除与肺水肿的研究进展
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摘要
肺水肿是急性肺损伤(ALI)病理进程中的中心环节,与肺泡毛细血管通透性增加和肺泡内液体清除减少有关。以往对肺泡毛细血管通透性导致的肺水肿研究较多,而对肺泡内液体清除在肺水肿形成中的作用关注不足。肺泡内液体清除受水通道蛋白、钠离子通道、钠钾ATP酶的影响。认识肺泡内液体清除机制有望能为临床医师治疗ALI提供参考。
Pulmonary edema is a so much hallmark event in pathology process of acute lung injury(ALI), which is associated with a increased alveolar-capillary permeability and decreased alveolar fluid clearance. The research of pulmonary edema mediated by alveolar-capillary permeability was much more than formation of pulmonary edema mediated by alveolar fluid clearance in past. Lung edema clearance is affected by aquaporin(AQP), epithelium Na+ channel(ENaC) and Na+-K+-ATPase. The understanding of how edema is cleared from the alveoli may provide a reference in treating ALI for clinicians.
Pulmonary edema is a so much hallmark event in pathology process of acute lung injury(ALI), which is associated with a increased alveolar-capillary permeability and decreased alveolar fluid clearance. The research of pulmonary edema mediated by alveolar-capillary permeability was much more than formation of pulmonary edema mediated by alveolar fluid clearance in past. Lung edema clearance is affected by aquaporin(AQP), epithelium Na+ channel(ENaC) and Na+-K+-ATPase. The understanding of how edema is cleared from the alveoli may provide a reference in treating ALI for clinicians.
引文
[1]Mutlu GM,Sznajder JI.Mechanisms of pulmonary edema clearance[J].Am J Physiol Lung Cell Mol Physiol,2005,289(5):L685-695.
[2]Ishibashi K,Hara S,Kondo S.Aquaporin water channels in mammals[J].Clin Exp Nephrol,2009,13(2):107-117.
[3]Verkman AS.Role of aquaporins in lung liquid physiology[J].Respir Physiol Neurobiol,2007,159(3):324-330.
[4]Ma T,Fukuda N,Song Y,et al.Lung fluid transport in aquaporin-5knockout mice[J].J Clin Invest,2000,105(1):93-100.
[5]Carter EP,Olveczky BP,Matthay MA,et al.High microvascular endothelial water permeability in mouse lung measured by a pleural surface fluorescence method[J].Biophys J,1998,74(4):2121-2128.
[6]Umenishi F,Carter EP,Yang B,et al.Sharp increase in rat lung water channel expression in the perinatal period[J].Am J Respir Cell Mol Biol,1996,15(5):673-679.
[7]King LS,Nielsen S,Agre P.Aquaporin-1 water channel protein in lung:ontogeny,steroid-induced expression,and distribution in rat[J].J Clin Invest,1996,97(10):2183-2191.
[8]Hoffert JD,Leitch V,Agre P,et al.Hypertonic induction of aquaporin-5 expression through an ERK-dependent pathway[J].J Biol Chem,2000,275(12):9070-9077.
[9]Sidhaye V,Hoffert JD,King LS.cAMP has distinct acute and chronic effects on aquaporin-5 in lung epithelial cells[J].J Biol Chem,2005,280(5):3590-3596.
[10]Jiao G,Li E,Yu R.Decreased expression of AQP1 and AQP5 in acute injured lungs in rats[J].Chin Med J(Engl),2002,115(7):963-967.
[11]Towne JE,Harrod KS,Krane CM,et al.Decreased expression of aquaporin(AQP)1 and AQP 5 in mouse lung after acute viral infection[J].Am J Respir Cell Mol Biol,2000,22(1):34-44.
[12]Xie YP,Chen CP,Wang JC,et al.Experimental study on the expression and function of aquaporin-1 and aquaporin-5 in rats with acute lung injury induced by lipopolysaccharide[J].Chin J Tuberc Respir Dis,2005,28(6):385-389.
[13]Towne JE,Krane CM,Bachurski CJ,et al.Tumor necrosis factor-alpha inhibits aquaporin expression in mouse lung epithelial cells[J].J Biol Chem,2001,276(22):18657-18664.
[14]Ben Y,Chen J,Zhu R,et al.Upregulation of AQP3 and AQP5induced by dexamethasone and ambroxol in A549 cells[J].Respir Physiol Neurobiol,2008,161(2):111-118.
[15]Ma TH,Zhang YW,Bi LT,et al.Reduced lung water transport rate associated with downregulation of aquaporin-1 and aquaporin-5 in aged mice[J].Clin Exp Pharmacol Physiol,2009,36(7):734-738.
[16]Wu XM,Wang HY,Li GF,et al.Dobutamine Enhances Alveolar Fluid Clearance in a Rat Model of Acute Lung Injury[J].Lung,2009,187(4):225-231.
[17]Jin LD,Wang LR,Wu LQ,et al.Effects of COX-2 inhibitor on ventilator-induced lung injury in rats[J].Int Immunopharmacol,2013,16(2):288-295.
[18]Zhao S,Li XN.Expression of aquaporin-1 and aquaporin-3 in lung tissue of rat model with ischemia-reperfusion injury[J].Chin Med J(Engl),2010,123(24):3711-3713.
[19]Li Z,Gao C,Wang Y,et al.Reducing pulmonary injury by hyperbaric oxygen preconditioning during simulated high altitude exposure in rats[J].J Trauma,2011,71(3):673-679.
[20]Hummler E,Barker P,Gatzy J,et al.Early death due to defective neonatalααlung liquid clearance inα-ENaC-deficient mice[J].Nat Genet,1996,12(3):325-328.
[21]Butterworth MB,Helman SI,Els WJ.cAMP-sensitive endocytic trafficking in A6 epithelia[J].Am J Physiol Cell Physiol,2001,280(4):C752-C762.
[22]Snyder PM.Liddle’s syndrome mutations disrupt cAMP-mediated translocation of the epithelial Na+channel to the cell surface[J].J Clin Invest,2000,105(1):45-53.
[23]McGraw DW,Fukuda N,James PF,et al.Targeted transgenic expression ofβ2-adrenergic receptors to type II cells increases alveolar fluid clearance[J].Am J Physiol Lung Cell Mol Physiol,2001,81(4):L895-L903.
[24]Frank J,Roux J,Kawakatsu H,et al.TGFβ1 decreasesαENaC expression and alveolar epithelial vectorial sodium and fluid transport via an ERK 1/2-dependent mechanism[J].J Biol Chem,2003,278(45):43939-43950.
[25]Galietta LJ,Folli C,Marchetti C,et al.Modification of transepithelial ion transport in human cultured bronchial epithelial cells by interferon-gamma[J].Am J Physiol Lung Cell Mol Physiol,2000,278(6):L1186-L1194.
[26]Galietta LJ,Pagesy P,Folli C,et al.IL-4 is a potent modulator of ion transport in the human bronchial epithelium in vitro[J].J Immunol,2002,168(2):839-845.
[27]Roux J,Kawakatsu H,Gartland B,et al.Interleukin-1βdecreases expression of the epithelial sodium channelα-subunit in alveolar epithelial cells via a p38 MAPK dependent signaling pathway[J].J Biol Chem,2005,280(19):18579-18589.
[28]Dagenais A,Fréchette R,Yamagata Y,et al.Downregulation of ENaC activity and expression by TNF-alpha in alveolar epithelial cells[J].Am J Physiol Lung Cell Mol Physiol,2004,286(2):L301-311.
[29]Cher CD,Armugam A,Lachumanan R,et al.Pulmonary inflammation and edema induced by phospholipase A2:global gene analysis and effects on aquaporins and Na+/K+ATPase[J].J Biol Chem,2003,278(33):31352-31360.
[30]Deng W,Li CY,Tong J,et al.Regulation of ENaC-mediated alveolar fluid clearance by insulin via PI3K/Akt pathway in LPS-induced acute lung injury[J].Respir Res,2012,13(5):29-33.
[31]Berger G,Guetta J,Klorin G,et al.Sepsis impairs alveolar epithelial function by down-regulating Na-K-ATPase pump[J].Am J Physiol Lung Cell Mol Physiol,2011,301(1):L23-L30.
[32]Ma T,Liu Z.Functions of aquaporin 1 andα-epithelial Na+channel in rat acute lung injury induced by acute ischemic kidney injury[J].Int Urol Nephrol,2013,45(4):1187-1196.
[33]Mairbaurl H,Mayer K,Kim KJ,et al.Hypoxia decreases active Na transport across primary rat alveolar epithelial cell monolayers[J].Am J Physiol Lung Cell Mol Physiol,2002,282(4):L659-L665.
[34]Planes C,Friedlander G,Loiseau A,et al.Inhibition of Na-KATPase activity after prolonged hypoxia in an alveolar epithelial cell line[J].Am J Physiol Lung Cell Mol Physiol,1996,271(1pt1):L70-L78.
[35]Adir Y,Welch LC,Dumasius V,et al.Overexpression of the Na-KATPase alpha2-subunit improves lung liquid clearance during ventilation-induced lung injury[J].Am J Physiol Lung Cell Mol Physiol,2008,294(6):L1233-L1237.
[36]Frank JA,Pittet JF,Lee H,et al.High tidal volume ventilation induces NOS2 and impairs cAMP-dependent air space fluid clearance[J].Am J Physiol Lung Cell Mol Physiol,2003,284(5):L791-798.
[37]Wang Q,Lian QQ,Li R,et al.Lipoxin A(4)activates alveolar epithelial sodium channel,Na,K-ATPase,and increases alveolar fluid clearance[J].Am J Respir Cell Mol Biol,2013,48(5):610-618.
[2]Ishibashi K,Hara S,Kondo S.Aquaporin water channels in mammals[J].Clin Exp Nephrol,2009,13(2):107-117.
[3]Verkman AS.Role of aquaporins in lung liquid physiology[J].Respir Physiol Neurobiol,2007,159(3):324-330.
[4]Ma T,Fukuda N,Song Y,et al.Lung fluid transport in aquaporin-5knockout mice[J].J Clin Invest,2000,105(1):93-100.
[5]Carter EP,Olveczky BP,Matthay MA,et al.High microvascular endothelial water permeability in mouse lung measured by a pleural surface fluorescence method[J].Biophys J,1998,74(4):2121-2128.
[6]Umenishi F,Carter EP,Yang B,et al.Sharp increase in rat lung water channel expression in the perinatal period[J].Am J Respir Cell Mol Biol,1996,15(5):673-679.
[7]King LS,Nielsen S,Agre P.Aquaporin-1 water channel protein in lung:ontogeny,steroid-induced expression,and distribution in rat[J].J Clin Invest,1996,97(10):2183-2191.
[8]Hoffert JD,Leitch V,Agre P,et al.Hypertonic induction of aquaporin-5 expression through an ERK-dependent pathway[J].J Biol Chem,2000,275(12):9070-9077.
[9]Sidhaye V,Hoffert JD,King LS.cAMP has distinct acute and chronic effects on aquaporin-5 in lung epithelial cells[J].J Biol Chem,2005,280(5):3590-3596.
[10]Jiao G,Li E,Yu R.Decreased expression of AQP1 and AQP5 in acute injured lungs in rats[J].Chin Med J(Engl),2002,115(7):963-967.
[11]Towne JE,Harrod KS,Krane CM,et al.Decreased expression of aquaporin(AQP)1 and AQP 5 in mouse lung after acute viral infection[J].Am J Respir Cell Mol Biol,2000,22(1):34-44.
[12]Xie YP,Chen CP,Wang JC,et al.Experimental study on the expression and function of aquaporin-1 and aquaporin-5 in rats with acute lung injury induced by lipopolysaccharide[J].Chin J Tuberc Respir Dis,2005,28(6):385-389.
[13]Towne JE,Krane CM,Bachurski CJ,et al.Tumor necrosis factor-alpha inhibits aquaporin expression in mouse lung epithelial cells[J].J Biol Chem,2001,276(22):18657-18664.
[14]Ben Y,Chen J,Zhu R,et al.Upregulation of AQP3 and AQP5induced by dexamethasone and ambroxol in A549 cells[J].Respir Physiol Neurobiol,2008,161(2):111-118.
[15]Ma TH,Zhang YW,Bi LT,et al.Reduced lung water transport rate associated with downregulation of aquaporin-1 and aquaporin-5 in aged mice[J].Clin Exp Pharmacol Physiol,2009,36(7):734-738.
[16]Wu XM,Wang HY,Li GF,et al.Dobutamine Enhances Alveolar Fluid Clearance in a Rat Model of Acute Lung Injury[J].Lung,2009,187(4):225-231.
[17]Jin LD,Wang LR,Wu LQ,et al.Effects of COX-2 inhibitor on ventilator-induced lung injury in rats[J].Int Immunopharmacol,2013,16(2):288-295.
[18]Zhao S,Li XN.Expression of aquaporin-1 and aquaporin-3 in lung tissue of rat model with ischemia-reperfusion injury[J].Chin Med J(Engl),2010,123(24):3711-3713.
[19]Li Z,Gao C,Wang Y,et al.Reducing pulmonary injury by hyperbaric oxygen preconditioning during simulated high altitude exposure in rats[J].J Trauma,2011,71(3):673-679.
[20]Hummler E,Barker P,Gatzy J,et al.Early death due to defective neonatalααlung liquid clearance inα-ENaC-deficient mice[J].Nat Genet,1996,12(3):325-328.
[21]Butterworth MB,Helman SI,Els WJ.cAMP-sensitive endocytic trafficking in A6 epithelia[J].Am J Physiol Cell Physiol,2001,280(4):C752-C762.
[22]Snyder PM.Liddle’s syndrome mutations disrupt cAMP-mediated translocation of the epithelial Na+channel to the cell surface[J].J Clin Invest,2000,105(1):45-53.
[23]McGraw DW,Fukuda N,James PF,et al.Targeted transgenic expression ofβ2-adrenergic receptors to type II cells increases alveolar fluid clearance[J].Am J Physiol Lung Cell Mol Physiol,2001,81(4):L895-L903.
[24]Frank J,Roux J,Kawakatsu H,et al.TGFβ1 decreasesαENaC expression and alveolar epithelial vectorial sodium and fluid transport via an ERK 1/2-dependent mechanism[J].J Biol Chem,2003,278(45):43939-43950.
[25]Galietta LJ,Folli C,Marchetti C,et al.Modification of transepithelial ion transport in human cultured bronchial epithelial cells by interferon-gamma[J].Am J Physiol Lung Cell Mol Physiol,2000,278(6):L1186-L1194.
[26]Galietta LJ,Pagesy P,Folli C,et al.IL-4 is a potent modulator of ion transport in the human bronchial epithelium in vitro[J].J Immunol,2002,168(2):839-845.
[27]Roux J,Kawakatsu H,Gartland B,et al.Interleukin-1βdecreases expression of the epithelial sodium channelα-subunit in alveolar epithelial cells via a p38 MAPK dependent signaling pathway[J].J Biol Chem,2005,280(19):18579-18589.
[28]Dagenais A,Fréchette R,Yamagata Y,et al.Downregulation of ENaC activity and expression by TNF-alpha in alveolar epithelial cells[J].Am J Physiol Lung Cell Mol Physiol,2004,286(2):L301-311.
[29]Cher CD,Armugam A,Lachumanan R,et al.Pulmonary inflammation and edema induced by phospholipase A2:global gene analysis and effects on aquaporins and Na+/K+ATPase[J].J Biol Chem,2003,278(33):31352-31360.
[30]Deng W,Li CY,Tong J,et al.Regulation of ENaC-mediated alveolar fluid clearance by insulin via PI3K/Akt pathway in LPS-induced acute lung injury[J].Respir Res,2012,13(5):29-33.
[31]Berger G,Guetta J,Klorin G,et al.Sepsis impairs alveolar epithelial function by down-regulating Na-K-ATPase pump[J].Am J Physiol Lung Cell Mol Physiol,2011,301(1):L23-L30.
[32]Ma T,Liu Z.Functions of aquaporin 1 andα-epithelial Na+channel in rat acute lung injury induced by acute ischemic kidney injury[J].Int Urol Nephrol,2013,45(4):1187-1196.
[33]Mairbaurl H,Mayer K,Kim KJ,et al.Hypoxia decreases active Na transport across primary rat alveolar epithelial cell monolayers[J].Am J Physiol Lung Cell Mol Physiol,2002,282(4):L659-L665.
[34]Planes C,Friedlander G,Loiseau A,et al.Inhibition of Na-KATPase activity after prolonged hypoxia in an alveolar epithelial cell line[J].Am J Physiol Lung Cell Mol Physiol,1996,271(1pt1):L70-L78.
[35]Adir Y,Welch LC,Dumasius V,et al.Overexpression of the Na-KATPase alpha2-subunit improves lung liquid clearance during ventilation-induced lung injury[J].Am J Physiol Lung Cell Mol Physiol,2008,294(6):L1233-L1237.
[36]Frank JA,Pittet JF,Lee H,et al.High tidal volume ventilation induces NOS2 and impairs cAMP-dependent air space fluid clearance[J].Am J Physiol Lung Cell Mol Physiol,2003,284(5):L791-798.
[37]Wang Q,Lian QQ,Li R,et al.Lipoxin A(4)activates alveolar epithelial sodium channel,Na,K-ATPase,and increases alveolar fluid clearance[J].Am J Respir Cell Mol Biol,2013,48(5):610-618.