{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,13]],"date-time":"2026-06-13T05:21:56Z","timestamp":1781328116543,"version":"3.54.1"},"reference-count":42,"publisher":"Portland Press Ltd.","issue":"5","content-domain":{"domain":["portlandpress.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2011,9,1]]},"abstract":"<jats:p>HHP (hypobaric hypoxia preconditioning) induces the overexpression of HSP70 (heat-shock protein 70), as well as tolerance to cerebral ischaemia. In the present study, we hypothesized that HHP would protect against HAE (high-altitude exposure)-induced acute lung injury and oedema via promoting the expression of HSP70 in lungs prior to the onset of HAE. At 2\u00a0weeks after the start of HHP, animals were exposed to a simulated HAE of 6000 m in a hypobaric chamber for 24\u00a0h. Immediately after being returned to ambient pressure, the non-HHP animals had higher scores of alveolar oedema, neutrophil infiltration and haemorrhage, acute pleurisy (e.g. increased exudate volume, increased numbers of polymorphonuclear cells and increased lung myeloperoxidase activity), increased pro-inflammatory cytokines [e.g. TNF-\u03b1 (tumour necrosis factor-\u03b1), IL (interleukin)-1\u03b2 and IL-6], and increased cellular ischaemia (i.e. glutamate and lactate\/pyruvate ratio) and oxidative damage [glycerol, NOx (combined nitrate+nitrite) and 2,3-dihydroxybenzoic acid] markers in the BALF (bronchoalveolar fluid). HHP, in addition to inducing overexpression of HSP70 in the lungs, significantly attenuated HAE-induced pulmonary oedema, inflammation, and ischaemic and oxidative damage in the lungs. The beneficial effects of HHP in preventing the occurrence of HAE-induced pulmonary oedema, inflammation, and ischaemic and oxidative damage was reduced significantly by pretreatment with a neutralizing anti-HSP70 antibody. In conclusion, HHP may attenuate the occurrence of pulmonary oedema, inflammation, and ischaemic and oxidative damage caused by HAE in part via up-regulating HSP70 in the lungs.<\/jats:p>","DOI":"10.1042\/cs20100596","type":"journal-article","created":{"date-parts":[[2011,5,20]],"date-time":"2011-05-20T19:40:23Z","timestamp":1305920423000},"page":"223-231","update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":45,"title":["Hypobaric hypoxia preconditioning attenuates acute lung injury during high-altitude exposure in rats via up-regulating heat-shock protein 70"],"prefix":"10.1042","volume":"121","author":[{"given":"Hung-Jung","family":"Lin","sequence":"first","affiliation":[{"name":"Department of Emergency Medicine, Chi Mei Medical Center, Tainan, Taiwan, Republic of China"},{"name":"Department of Biotechnology, Southern Taiwan University, Tainan, Taiwan, Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chia-Ti","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Emergency Medicine, Chi Mei Medical Center, Tainan, Taiwan, Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ko-Chi","family":"Niu","sequence":"additional","affiliation":[{"name":"Department of Biotechnology, Southern Taiwan University, Tainan, Taiwan, Republic of China"},{"name":"Department of Hyperbaric Oxygen, Chi Mei Medical Center, Tainan, Taiwan, Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chungjin","family":"Gao","sequence":"additional","affiliation":[{"name":"Department of Hyperbaric Oxygen, Beijing Chaoyang Hospital, Beijing, People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhuo","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Hyperbaric Oxygen, Beijing Chaoyang Hospital, Beijing, People's Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mao-Tsun","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Medical Research, Chi Mei Medical Center, Tainan, Taiwan, Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ching-Ping","family":"Chang","sequence":"additional","affiliation":[{"name":"Department of Biotechnology, Southern Taiwan University, Tainan, Taiwan, Republic of China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"288","published-online":{"date-parts":[[2011,5,20]]},"reference":[{"key":"2021113010191453600_B1","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1016\/j.pcad.2010.02.005","article-title":"Lung fluid movements in hypoxia","volume":"52","author":"Sartori","year":"2010","journal-title":"Prog. Cardiovasc. Dis."},{"key":"2021113010191453600_B2","doi-asserted-by":"crossref","first-page":"1713","DOI":"10.1161\/01.CIR.99.13.1713","article-title":"Augmented sympathetic activation during short-term hypoxia and high-altitude exposure in subjects susceptible to high-altitude pulmonary edema","volume":"99","author":"Duplain","year":"1999","journal-title":"Circulation"},{"key":"2021113010191453600_B3","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1089\/ham.2008.1053","article-title":"Transpulmonary plasma ET-1 and nitrite differences in high altitude pulmonary hypertension","volume":"10","author":"Berger","year":"2009","journal-title":"High Alt. Med. Biol."},{"key":"2021113010191453600_B4","doi-asserted-by":"crossref","first-page":"1929","DOI":"10.1152\/jappl.1988.65.5.1929","article-title":"Atrial natriuretic peptide in acute mountain sickness","volume":"65","author":"B\u00e4rtsch","year":"1988","journal-title":"J. Appl. Physiol."},{"key":"2021113010191453600_B5","doi-asserted-by":"crossref","first-page":"624","DOI":"10.1056\/NEJM199603073341003","article-title":"Inhaled nitric oxide for high-altitude pulmonary edema","volume":"334","author":"Scherrer","year":"1996","journal-title":"N. Engl. J. Med."},{"key":"2021113010191453600_B6","doi-asserted-by":"crossref","first-page":"368","DOI":"10.1164\/ajrccm.163.2.2001134","article-title":"Hypoxia decreases exhaled nitric oxide in mountaineers susceptible to high-altitude pulmonary edema","volume":"163","author":"Busch","year":"2001","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"2021113010191453600_B7","doi-asserted-by":"crossref","first-page":"2228","DOI":"10.1001\/jama.287.17.2228","article-title":"Pathogenesis of high-altitude pulmonary edema: inflammation is not an etiologic factor","volume":"287","author":"Swenson","year":"2002","journal-title":"JAMA, J. Am. Med. Assoc."},{"key":"2021113010191453600_B8","doi-asserted-by":"crossref","first-page":"763","DOI":"10.1164\/rccm.200504-654OC","article-title":"Hypoxia impairs systemic endothelial function in individuals prone to high-altitude pulmonary edema","volume":"172","author":"Berger","year":"2005","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"2021113010191453600_B9","doi-asserted-by":"crossref","first-page":"H331","DOI":"10.1152\/ajpheart.00583.2009","article-title":"Low-dose sodium nitrite vasodilates hypoxic human pulmonary vasculature by a means that is not dependent on a simultaneous elevation in plasma nitrite","volume":"298","author":"Ingram","year":"2010","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"2021113010191453600_B10","doi-asserted-by":"crossref","first-page":"807","DOI":"10.1113\/expphysiol.2006.033506","article-title":"Oxygen sensing by mitochondria at complex III: the paradox of increased reactive oxygen species during hypoxia","volume":"91","author":"Guzy","year":"2006","journal-title":"Exp. Physiol."},{"key":"2021113010191453600_B11","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1113\/expphysiol.2007.041236","article-title":"Oxygen sensing in hypoxic pulmonary vasoconstriction: using new tools to answer an age-old question","volume":"93","author":"Waypa","year":"2008","journal-title":"Exp. Physiol."},{"key":"2021113010191453600_B12","first-page":"149","article-title":"Selective vulnerability in brain hypoxia","volume":"6","author":"Cervos-Navarro","year":"1991","journal-title":"Crit. Rev. Neurobiol."},{"key":"2021113010191453600_B13","doi-asserted-by":"crossref","first-page":"1135","DOI":"10.1152\/physrev.1991.71.4.1135","article-title":"Physiological adaptation to high altitude: oxygen transport in mammals and birds","volume":"71","author":"Monge","year":"1991","journal-title":"Physiol. Rev."},{"key":"2021113010191453600_B14","doi-asserted-by":"crossref","first-page":"896","DOI":"10.1152\/jappl.1994.77.2.896","article-title":"Hypoxia increases glucose transport at blood\u2013brain barrier in rats","volume":"77","author":"Harik","year":"1994","journal-title":"J. Appl. Physiol."},{"key":"2021113010191453600_B15","doi-asserted-by":"crossref","first-page":"2238","DOI":"10.1152\/jappl.1992.72.6.2238","article-title":"Brain adaptation to chronic hypobaric hypoxia in rats","volume":"72","author":"LaManna","year":"1992","journal-title":"J. Appl. Physiol."},{"key":"2021113010191453600_B16","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1016\/0006-8993(90)90189-I","article-title":"\u2018Ischemic tolerance\u2019 phenomenon found in the brain","volume":"528","author":"Kitagawa","year":"1990","journal-title":"Brain Res."},{"key":"2021113010191453600_B17","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1023\/A:1021119112927","article-title":"The adaptive effects of hypoxic preconditioning of brain neurons","volume":"33","author":"Samoilov","year":"2003","journal-title":"Neurosci. Behav. Physiol."},{"key":"2021113010191453600_B18","article-title":"Reducing pulmonary injury by hyperbaric oxygen preconditioning during simulated high altitude exposure in rats","author":"Li","year":"2011","journal-title":"J. Trauma"},{"key":"2021113010191453600_B19","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1046\/j.1440-1681.2002.03680.x","article-title":"Chronic hypoxia preconditioning increases survival in rats suffering from heatstroke","volume":"29","author":"Wen","year":"2002","journal-title":"Clin. Exp. Pharmacol. Physiol."},{"key":"2021113010191453600_B20","doi-asserted-by":"crossref","first-page":"4837","DOI":"10.1113\/jphysiol.2010.194704","article-title":"High-altitude pulmonary hypertension is associated with a free radical-mediated reduction in pulmonary nitric oxide bioavailability","volume":"23","author":"Bailey","year":"2010","journal-title":"J. Physiol."},{"key":"2021113010191453600_B21","doi-asserted-by":"crossref","first-page":"748","DOI":"10.1007\/BF02254359","article-title":"Neuroprotective role of heat shock protein 70 in the rostral ventrolateral medulla during acute mevinphos intoxication in the rat","volume":"11","author":"Chang","year":"2004","journal-title":"J. Biomed. Sci."},{"key":"2021113010191453600_B22","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.resp.2004.05.001","article-title":"The role of aquaporin-1 (AQP1) expression in a murine model of lipopolysaccharide-induced acute lung injury","volume":"142","author":"Su","year":"2004","journal-title":"Respir. Physiol. Neurobiol."},{"key":"2021113010191453600_B23","doi-asserted-by":"crossref","first-page":"388","DOI":"10.1097\/00024382-200304000-00016","article-title":"Hypothermia attenuates circulatory shock and cerebral ischemia in experimental heatstroke","volume":"19","author":"Chou","year":"2003","journal-title":"Shock"},{"key":"2021113010191453600_B24","doi-asserted-by":"crossref","first-page":"1234","DOI":"10.1046\/j.1471-4159.1997.68031234.x","article-title":"Simultaneous measurement of nitrite and nitrate levels as indices of nitric oxide release in the cerebellum of conscious rats","volume":"68","author":"Yamada","year":"1997","journal-title":"J. Neurochem."},{"key":"2021113010191453600_B25","first-page":"53","article-title":"Consecutive evaluation of nitric oxide production after transient cerebral ischemia in the rat hippocampus using in vivo brain microdialysis. Neurosci","volume":"240","author":"Togashi","year":"1998","journal-title":"Lett."},{"key":"2021113010191453600_B26","doi-asserted-by":"crossref","first-page":"724","DOI":"10.1111\/j.2042-7158.1997.tb06100.x","article-title":"Use of microdialysis for in vivo monitoring of hydroxyl free-radical generation in the rat","volume":"49","author":"Obata","year":"1997","journal-title":"J. Pharm. Pharmacol."},{"key":"2021113010191453600_B27","doi-asserted-by":"crossref","first-page":"790","DOI":"10.1161\/hs0102.100208","article-title":"Oxidative stress in rats with heatstroke-induced cerebral ischemia","volume":"33","author":"Yang","year":"2002","journal-title":"Stroke"},{"key":"2021113010191453600_B28","first-page":"1065","article-title":"Neutrophil alveolitis following endotoxemia. Enhancement by previous exposure to hyperoxia","volume":"130","author":"Rinaldo","year":"1984","journal-title":"Am. Rev. Respir. Dis."},{"key":"2021113010191453600_B29","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1258\/002367792780809020","article-title":"Intratracheal aerosolization of endotoxin in the rat: a model of the adult respiratory distress syndrome (ARDS)","volume":"26","author":"Wheeldon","year":"1992","journal-title":"Lab. Anim."},{"key":"2021113010191453600_B30","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1016\/S0012-3692(15)37965-4","article-title":"Effects of various body temperatures after lipopolysaccharide-induced lung injury in rats","volume":"128","author":"Chu","year":"2005","journal-title":"Chest"},{"key":"2021113010191453600_B31","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1165\/ajrcmb.10.2.8110470","article-title":"Cytokine expression by neutrophils and macrophages in vivo: endotoxin induces tumor necrosis factor-\u03b1, macrophage inflammatory protein-2, interleukin-1\u03b2, and interleukin-6 but not RANTES or transforming growth factor-\u03b21 mRNA expression in acute lung inflammation","volume":"10","author":"Xing","year":"1994","journal-title":"Am. J. Respir. Cell Mol. Biol."},{"key":"2021113010191453600_B32","doi-asserted-by":"crossref","first-page":"1850","DOI":"10.1164\/ajrccm.153.6.8665045","article-title":"Proinflammatory activity in bronchoalveolar lavage fluids from patients with ARDS, a prominent role for interleukin-1","volume":"153","author":"Pugin","year":"1996","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"2021113010191453600_B33","doi-asserted-by":"crossref","first-page":"1917","DOI":"10.1152\/jappl.1996.81.5.1917","article-title":"Evidence against an increase in capillary permeability in subjects exposed to high altitude","volume":"81","author":"Kleger","year":"1996","journal-title":"J. Appl. Physiol."},{"key":"2021113010191453600_B34","doi-asserted-by":"crossref","first-page":"1393","DOI":"10.1378\/chest.117.5.1393","article-title":"(2000) Urinary leukotriene E4 levels are not increased prior to high-altitude pulmonary edema","volume":"117","author":"B\u00e4rtsch","journal-title":"Chest"},{"key":"2021113010191453600_B35","doi-asserted-by":"crossref","first-page":"1050","DOI":"10.1016\/S0891-5849(02)00794-3","article-title":"Lipid peroxidation and protein oxidation in Alzheimer's disease brain: potential causes and consequences involving amyloid \u03b2-peptide-associated free radical oxidative stress","volume":"32","author":"Butterfield","year":"2002","journal-title":"Free Radical Biol. Med."},{"key":"2021113010191453600_B36","doi-asserted-by":"crossref","first-page":"709","DOI":"10.1016\/j.neuint.2006.06.002","article-title":"Hypobaric hypoxia induces oxidative stress in rat brain","volume":"49","author":"Maiti","year":"2006","journal-title":"Neurochem. Int."},{"key":"2021113010191453600_B37","doi-asserted-by":"crossref","first-page":"437","DOI":"10.1016\/j.resuscitation.2006.11.003","article-title":"Resuscitation from experimental heatstroke by brain cooling therapy","volume":"73","author":"Hsiao","year":"2007","journal-title":"Resuscitation"},{"key":"2021113010191453600_B38","doi-asserted-by":"crossref","first-page":"210","DOI":"10.1097\/01.shk.0000223124.49265.10","article-title":"Brain cooling causes attenuation of cerebral oxidative stress, systemic inflammation, activated coagulation, and tissue ischemia\/injury during heat stroke","volume":"26","author":"Hsu","year":"2006","journal-title":"Shock"},{"key":"2021113010191453600_B39","doi-asserted-by":"crossref","first-page":"284","DOI":"10.1097\/SHK.0b013e3180311e60","article-title":"Effect of brain cooling on brain ischemia and damage markers after fluid percussion brain injury in rats","volume":"28","author":"Chio","year":"2007","journal-title":"Shock"},{"key":"2021113010191453600_B40","doi-asserted-by":"crossref","first-page":"921","DOI":"10.1111\/j.1471-4159.2010.06969.x","article-title":"Therapeutic evaluation of etanercept in a model of traumatic brain injury","volume":"115","author":"Chio","year":"2010","journal-title":"J. Neurochem."},{"key":"2021113010191453600_B41","doi-asserted-by":"crossref","first-page":"555","DOI":"10.1172\/JCI4138","article-title":"Lung fluid transport in aquaporin-1 and aquaporin-4 knockout mice","volume":"103","author":"Bai","year":"1999","journal-title":"J. Clin. Invest."},{"key":"2021113010191453600_B42","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1172\/JCI8258","article-title":"Lung fluid transport in aquaporin-5 knockout mice","volume":"105","author":"Ma","year":"2000","journal-title":"J. Clin. 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