• 1 復(fù)旦大學(xué)附屬中山醫(yī)院呼吸內(nèi)科（上海 200032）;;
  • 2 西藏軍區(qū)總醫(yī)院高原病研究中心;

高原性肺水腫(HAPE)是人們由低海拔快速進(jìn)入高海拔地區(qū)（一般3 000 m以上）后2～5 d內(nèi)發(fā)生的非心源性肺水腫，是一種重型急性高原病，起病急、進(jìn)展快、危害大，若不及時(shí)救治，可能危及生命。經(jīng)過多年努力，對其發(fā)病機(jī)制及治療進(jìn)行了大量研究，取得了一些結(jié)果，但仍有許多未明之處，本文綜述近年在此領(lǐng)域的研究進(jìn)展，以期對HAPE的研究具有一定推動(dòng)作用。

引用本文： 王桂芳 ,白春學(xué),李素芝. 高原性肺水腫發(fā)病機(jī)制的研究進(jìn)展. 中國呼吸與危重監(jiān)護(hù)雜志, 2008, 08(4): 318-320. doi: 復(fù)制

1. Yamashita K，Discher DJ，Hu J，et al．Molecular regulation of the endothelin-1 gene by hypoxia.Contributions of hypoxia-inducible factor-1，activator protein-1，GATA-2，AND p300/CBP.J Biol Chem，2001，276：12645-12653.
2. Carpenter TC，Schomberg S，Stenmark KR.Endothelin-mediated increases in lung VEGF content promote vascular leak in young rats exposed to viral infection and hypoxia.Am J Physiol Lung Cell Mol Physiol，2005，289：L1075-1082.
3. Modesti PA，Vanni S，Morabito M，et al．Role of endothelin-1 in exposure to high altitude：Acute Mountain Sickness and Endothelin-1 (ACME-1) study.Circulation，2006，114：1410-1416.
4. Jain M，Sznajder JI.Effects of hypoxia on the alveolar epithelium.Proc Am Thorac Soc，2005，2：202-205.
5. Robert JK，John RS，Norimasa F，et al.Lung overexpression of the vascular endothelial growth factor gene induces pulmonary edema．Am J Respir Cel Mol Biol，2000，22：657.
6. Antonetti DA，Barber AJ，Holinger LA，et al.Vascular endothelial growth factor induces rapid phosphorylation of tight junction proteins occudlin and zonular occudlin 1.J Biol Chem，1999，274：234-263.
7. Bouvry D，Planes C，Malbert-Colas L，et al.Hypoxia-induced cytoskeleton disruption in alveolar epithelial cells.Am J Respir Cell Mol Biol，2006，35：519-527.
8. Rachel LZ，Michael AM.Bench-to-bedside review：The role of the alveolar epithelium in the resolution of pulmonary edema in acute lung injury.Critical Care，2004，8：469-477.
9. Modesti PA，Vanni S，Morabito M，et al.Pulmonary blood flow heterogeneity during hypoxia and high-altitude pulmonary edema.Am J Respir Crit Care Med，2005，171：83-87.
10. Densmore JC，Signorino PR，Ou J，et al.Endothelium-derived microparticles induce endothelial dysfunction and acute lung injury.Shock，2006，26：464-471.
11. Jain M，Sznajder JI.Effects of hypoxia on the alveolar epithelium.Proc Am Thorac Soc，2005，2：202-205.
12. Swenson ER，Maggiorini M，Mongovin S，et al.Pathogenesis of high-altitude pulmonary edema：inflammation is not an etiologic factor.JAMA，2002，287：2228-2235.
13. 沈俊，王慶，張慧，等.急性中、重度低壓缺氧對大鼠血腦屏障通透性的影響.中華航空航天醫(yī)學(xué)雜志，2000，11：233-235.
14. Carole Planès，Brigitte Escoubet，Marcel Blot-Chabaud，et al.Hypoxia down regulates expression and activity of epithelial sodium channels in rat alveolar epithelial cells.Am J Respir Cell Mol Biol，1997，17：508-518.
15. Raina S，Preston GM，Guggino WB，et al.Molecular cloning and characterization of an aquaporin cDNA from salivary，lacrimal，and respiratory tissues.J Biol Chem，1995，270：1908-1912.
16. Bai C，F(xiàn)ukuda N，Song Y，et al.Lung fluid transport in aquaporin-1 and aquaporin-4 knockout mice.J Clin Invest，1999，103：555-561.
17. Ma T，F(xiàn)ukuda N，Song Y，et al.Role of AQP 5 in lung fluid transport.J Clin Invest，2000，105：93-100.
18. Grazia PN，Miduturu S，Wei Li，et al.New possible roles for aquaporin-4 in astrocytes：cell cytoskeleton and functional relationship with connexin 43.FASEB J，2005，19：1674-1676.
19. Beiyun Zhou，David K Ann，Xian Li，et al.Hypertonic induction of aquaporin-5：novel role of hypoxia inducible factor-1.Am J Physiol Cell Physiol，2007，292：C1280-C1290.
20. Minakata Y，Suzuki S，Grygorczyk C，et al.Impact of beta-adrenergic agonist on Na channel and Na-K-ATPase expression in alveolar type II cells.Am J Physiol，1998，275：1414- 1422.
21. Maggiorini M，Brunner-La Rocca HP，Peth S，et al.Both tadalafil and dexamethasone may reduce the incidence of high altitude pulmonary edema：a randomized trial.Ann Intern Med，2006，145：497-506.
22. Leroy C，Prive A，Bourret JC，et al.Regulation of ENaC and CFTR expression with K-channel modulators and effect on fluid absorption across alveolar epithelial cells.Am J Physiol Lung Cell Mol Physiol，2006，291：L1207- L1219.
23. Marco Maggiorini，Hans-Peter Brunner-La Rocca，Simon Peth，et al.Both Tadalafil and Dexamethasone May Reduce the Incidence of High-Altitude Pulmonary Edema A Randomized Trial.Ann Intern Med，2006，145：497-506.
  1. 1. Yamashita K，Discher DJ，Hu J，et al．Molecular regulation of the endothelin-1 gene by hypoxia.Contributions of hypoxia-inducible factor-1，activator protein-1，GATA-2，AND p300/CBP.J Biol Chem，2001，276：12645-12653.
  2. 2. Carpenter TC，Schomberg S，Stenmark KR.Endothelin-mediated increases in lung VEGF content promote vascular leak in young rats exposed to viral infection and hypoxia.Am J Physiol Lung Cell Mol Physiol，2005，289：L1075-1082.
  3. 3. Modesti PA，Vanni S，Morabito M，et al．Role of endothelin-1 in exposure to high altitude：Acute Mountain Sickness and Endothelin-1 (ACME-1) study.Circulation，2006，114：1410-1416.
  4. 4. Jain M，Sznajder JI.Effects of hypoxia on the alveolar epithelium.Proc Am Thorac Soc，2005，2：202-205.
  5. 5. Robert JK，John RS，Norimasa F，et al.Lung overexpression of the vascular endothelial growth factor gene induces pulmonary edema．Am J Respir Cel Mol Biol，2000，22：657.
  6. 6. Antonetti DA，Barber AJ，Holinger LA，et al.Vascular endothelial growth factor induces rapid phosphorylation of tight junction proteins occudlin and zonular occudlin 1.J Biol Chem，1999，274：234-263.
  7. 7. Bouvry D，Planes C，Malbert-Colas L，et al.Hypoxia-induced cytoskeleton disruption in alveolar epithelial cells.Am J Respir Cell Mol Biol，2006，35：519-527.
  8. 8. Rachel LZ，Michael AM.Bench-to-bedside review：The role of the alveolar epithelium in the resolution of pulmonary edema in acute lung injury.Critical Care，2004，8：469-477.
  9. 9. Modesti PA，Vanni S，Morabito M，et al.Pulmonary blood flow heterogeneity during hypoxia and high-altitude pulmonary edema.Am J Respir Crit Care Med，2005，171：83-87.
  10. 10. Densmore JC，Signorino PR，Ou J，et al.Endothelium-derived microparticles induce endothelial dysfunction and acute lung injury.Shock，2006，26：464-471.
  11. 11. Jain M，Sznajder JI.Effects of hypoxia on the alveolar epithelium.Proc Am Thorac Soc，2005，2：202-205.
  12. 12. Swenson ER，Maggiorini M，Mongovin S，et al.Pathogenesis of high-altitude pulmonary edema：inflammation is not an etiologic factor.JAMA，2002，287：2228-2235.
  13. 13. 沈俊，王慶，張慧，等.急性中、重度低壓缺氧對大鼠血腦屏障通透性的影響.中華航空航天醫(yī)學(xué)雜志，2000，11：233-235.
  14. 14. Carole Planès，Brigitte Escoubet，Marcel Blot-Chabaud，et al.Hypoxia down regulates expression and activity of epithelial sodium channels in rat alveolar epithelial cells.Am J Respir Cell Mol Biol，1997，17：508-518.
  15. 15. Raina S，Preston GM，Guggino WB，et al.Molecular cloning and characterization of an aquaporin cDNA from salivary，lacrimal，and respiratory tissues.J Biol Chem，1995，270：1908-1912.
  16. 16. Bai C，F(xiàn)ukuda N，Song Y，et al.Lung fluid transport in aquaporin-1 and aquaporin-4 knockout mice.J Clin Invest，1999，103：555-561.
  17. 17. Ma T，F(xiàn)ukuda N，Song Y，et al.Role of AQP 5 in lung fluid transport.J Clin Invest，2000，105：93-100.
  18. 18. Grazia PN，Miduturu S，Wei Li，et al.New possible roles for aquaporin-4 in astrocytes：cell cytoskeleton and functional relationship with connexin 43.FASEB J，2005，19：1674-1676.
  19. 19. Beiyun Zhou，David K Ann，Xian Li，et al.Hypertonic induction of aquaporin-5：novel role of hypoxia inducible factor-1.Am J Physiol Cell Physiol，2007，292：C1280-C1290.
  20. 20. Minakata Y，Suzuki S，Grygorczyk C，et al.Impact of beta-adrenergic agonist on Na channel and Na-K-ATPase expression in alveolar type II cells.Am J Physiol，1998，275：1414- 1422.
  21. 21. Maggiorini M，Brunner-La Rocca HP，Peth S，et al.Both tadalafil and dexamethasone may reduce the incidence of high altitude pulmonary edema：a randomized trial.Ann Intern Med，2006，145：497-506.
  22. 22. Leroy C，Prive A，Bourret JC，et al.Regulation of ENaC and CFTR expression with K-channel modulators and effect on fluid absorption across alveolar epithelial cells.Am J Physiol Lung Cell Mol Physiol，2006，291：L1207- L1219.
  23. 23. Marco Maggiorini，Hans-Peter Brunner-La Rocca，Simon Peth，et al.Both Tadalafil and Dexamethasone May Reduce the Incidence of High-Altitude Pulmonary Edema A Randomized Trial.Ann Intern Med，2006，145：497-506.