不同海拔地区急性暴露的健康人急性高原病发生情况及血清ET-1、ADMA、VEGF水平变化
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摘要
目的观察急进不同海拔地区的健康人群急性高原病(AMS)发生情况及血清内皮素1(ET-1)、非对称性二甲基精氨酸(ADMA)、血管内皮生长因子(VEGF)水平变化,探讨在不同海拔地区急性暴露对健康人血管内皮功能的影响。方法在平原地区招募健康志愿者45人,从平原(海拔400 m)出发,途经西宁市(海拔2 260 m)、刚察县(海拔3 260 m)及玛多县(海拔4 270 m)。400 m到2 260 m通过乘坐火车到达,时间28 h,停留72 h后进行路易斯湖评分体系(LLSS)判定受试者AMS发生情况;2 260 m以后乘坐大巴车迁移,途中时间分别为10、18 h,在3 260 m、4 270 m海拔各停留72 h进行LLSS评分。分别于从平原进入高海拔地区前24 h和进入不同海拔地区后72 h采集静脉血标本,采用ELISA法检测血清ET-1、ADMA、VEGF。结果所有受试者在不同海拔地区均未发生AMS。随着海拔升高,受试者血清ET-1、VEGF、ADMA水平逐渐下降,其中进入海拔3 260、4 270 m地区时受试者血清ET-1、VEGF、ADMA水平低于进入海拔400 m、2 260 m地区时,在海拔4 270 m地区时血清ET-1、VEGF、ADMA水平低于进入海拔3 260 m地区时(P均<0.05)。吸烟者与不吸烟者进入不同海拔地区时血清ET-1、VEGF、ADMA水平差异均无统计学意义。吸烟者或不吸烟者进入海拔4 270 m地区时血清ET-1、VEGF、ADMA水平低于同组进入海拔3 260 m地区时(P均<0.05)。是否吸烟与不同海拔因素之间无交互作用,不同海拔对ET-1、VEGF、ADMA水平的影响与吸烟因素无关。结论健康人由平原地区通过梯度海拔进入高海拔地区可能有助于降低AMS的发生率,在此过程中血清ET-1、VEGF、ADMA水平呈降低趋势。进入高海拔地区导致的血清ET-1、VEGF、ADMA水平变化与吸烟因素无关。
Objective To observe the occurrence of acute mountain sickness(AMS), the changes in levels of endothelin-1(ET-1), asymmetric dimethylarginine(ADMA), vascular endothelial growth factor(VEGF) in blood of healthy people after they gradually entered the high altitude area from low altitude, and to investigate the effects of acute exposure at different altitudes on vascular endothelial function in healthy individuals. Methods Forty-five healthy volunteers were recruited from the plains, starting from the plain(400 m above sea level), passing through Xining City(2260 m), Gangcha County(3260 m) and Maduo County(4 270 m). From 400 to 2260 m, it took us 28 hours to arrive by train, and the Lake Louise Score System(LLSS) was used to determine the occurrence of AMS in subjects after staying for 72 h. After 2260 m, we migrated by bus with 10 and 18 h, the LLSS was was used to determine the occurrence of AMS both at 3260 m and 4270 m after staying for 72 h. Venous blood samples were collected from the subjects using vacuum blood collection tubes in the first 24 h before entering the high-altitude area and 72 h after entering different altitudes. The levels of ET-1, ADMA, and VEGF were measured by ELISA.Results All subjects did not develop AMS at different altitudes. As the altitude increased, the serum levels of ET-1, VEGF and ADMA decreased gradually. The serum ET-1, VEGF, and ADMA levels in the subjects at 3 260 and 4 270 m above the altitude were lower than those at the altitude of 400 m. In the 2 260 m area, the serum ET-1, VEGF, and ADMA levels were lower than those at the altitude of 3 260 m(all P<0.05). There was no significant difference in the serum ET-1, VEGF, or ADMA levels between smokers and non-smokers entering different altitudes. When the smokers or non-smokers entered the altitude of 4270 m, the serum levels of ET-1, VEGF, and ADMA were lower than those of the same group at 3260 m(all P<0.05). There was no interaction between smoking and different altitude factors. The effects of different altitudes on ET-1, VEGF and ADMA levels were not related to smoking.Conclusions For healthy people, entering the high altitudes from the plains through gradient elevations helps to reduce the incidence of AMS, during which, the serum ET-1, VEGF, and ADMA levels are decreasing. Changes in serum ET-1, VEGF, and ADMA levels at high altitudes are not associated with smoking.
Objective To observe the occurrence of acute mountain sickness(AMS), the changes in levels of endothelin-1(ET-1), asymmetric dimethylarginine(ADMA), vascular endothelial growth factor(VEGF) in blood of healthy people after they gradually entered the high altitude area from low altitude, and to investigate the effects of acute exposure at different altitudes on vascular endothelial function in healthy individuals. Methods Forty-five healthy volunteers were recruited from the plains, starting from the plain(400 m above sea level), passing through Xining City(2260 m), Gangcha County(3260 m) and Maduo County(4 270 m). From 400 to 2260 m, it took us 28 hours to arrive by train, and the Lake Louise Score System(LLSS) was used to determine the occurrence of AMS in subjects after staying for 72 h. After 2260 m, we migrated by bus with 10 and 18 h, the LLSS was was used to determine the occurrence of AMS both at 3260 m and 4270 m after staying for 72 h. Venous blood samples were collected from the subjects using vacuum blood collection tubes in the first 24 h before entering the high-altitude area and 72 h after entering different altitudes. The levels of ET-1, ADMA, and VEGF were measured by ELISA.Results All subjects did not develop AMS at different altitudes. As the altitude increased, the serum levels of ET-1, VEGF and ADMA decreased gradually. The serum ET-1, VEGF, and ADMA levels in the subjects at 3 260 and 4 270 m above the altitude were lower than those at the altitude of 400 m. In the 2 260 m area, the serum ET-1, VEGF, and ADMA levels were lower than those at the altitude of 3 260 m(all P<0.05). There was no significant difference in the serum ET-1, VEGF, or ADMA levels between smokers and non-smokers entering different altitudes. When the smokers or non-smokers entered the altitude of 4270 m, the serum levels of ET-1, VEGF, and ADMA were lower than those of the same group at 3260 m(all P<0.05). There was no interaction between smoking and different altitude factors. The effects of different altitudes on ET-1, VEGF and ADMA levels were not related to smoking.Conclusions For healthy people, entering the high altitudes from the plains through gradient elevations helps to reduce the incidence of AMS, during which, the serum ET-1, VEGF, and ADMA levels are decreasing. Changes in serum ET-1, VEGF, and ADMA levels at high altitudes are not associated with smoking.
引文
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[13] Bailey DM, Kleger GR, Holzgraefe M, et al. Pathophysiological significance of peroxidative stress, neuronal damage, and membrane permeability in acute mountain sickness[J]. J Appl Physiol, 2004,96(4):1459-1463.
[14] Schmerbach K, Patzak A. Pathophysiological mechanisms in acute mountain sickness[J]. Acta Physiologica, 2013,209(4):246-249.
[15] 薛增军,李英悦.从高原急进特高海拔地区人体血浆内皮素-1水平的变化及其意义[J].高原医学杂志,1997,7(4):23-24.
[16] Liang J, Zhang Z, Liang L, et al. HIF-1a regulated tongue squamous cell carcinoma cell growth via regulating VEGF expression in a xenograft model[J]. Ann Translat Med, 2014, 2(9): 92-98.
[17] Dorward DA, Thompson AA, Baillie JK, et al. Change in plasma vascular endothelial growth factor during onset and recovery from acute mountain sickness[J]. Respirat Med, 2007,101(3):587-594.
[18] 何显菁,廖树森.非对称性二甲基精氨酸与心血管疾病关系的研究进展[J].实用心脑肺血管病杂志,2016,24(3):1-3.
[19] Burtscher M, Brandstatter E, Gatterer H. Preacclimatization insimulated altitudes[J]. Sleep Breath, 2008,12(2):109-114.
[20] 高炜,张世范,赵秋玲,等.急性高原病量化评分系统的前瞻性评估[J].第四军医大学学报,2008,29(2):151-153.
[2] Brown DE, Beall CM, Strohl KP, et al. Exhaled nitric oxide decreases upon acute exposure to high-altitude hypoxia[J]. Am J Hum Biol, 2010,18(2):196-202.
[3] Han Y, Yan G, Wang Q, et al. Predominantrole of vasoconstrictors over dilatators derived from arachidonic acid in hypoxic pulmonary vasoconstriction[J]. Mol Med Rep, 2013,8(4):1263-1271.
[4] Cargill RI, Kiely DG, Clark RA. Hypoxaemia and release of endothelin-1[J]. Thorax, 1995,50(12):1308-1310.
[5] Modesti PA, Vanni S, Morabito M. Role of endothelin-1 in exposure to high altitude: Acute Mountain Sickness and Endothelin-1 (ACME-1) study[J]. Circulation, 2006,114(13):1410-1416.
[6] Farber HW, Barnett HF. Differences in prostaglandin metabolism in cultured aortic and pulmonar y arterial endothelial cells exposed to acute and chronic hypoxia[J]. Circ Res, 1991,68(5):1446-1457.
[7] 王育伟,王荣,谢华,等.急性炎症因子临床意义与检测及其在高原医药学中的应用展望[J].解放军医药杂志,2013,25(6):28-32.
[8] 李明,张继航,卞士柱,等.氧输送量及其代偿因素与急性高原病的关系研究[J].解放军医学杂志,2013,38(3):245-248.
[9] 华明磊,丁辉.进入高原前后急性高原病患者血浆血管内皮生长因子的变化[J].武警后勤学院学报(医学版),2014,23(2):100-102.
[10] Meier D, Collet TH, Locatelli I, et al. Does this patient have acute mountain sickness The rational clinical examination systematic review[J]. JAMA, 2017,318(18):1810-1819.
[11] Luks AM, Swenson ER, Bartsch P. Acute high-altitude sickness[J]. European respiratory review : an official journal of the European Respiratory Society, 2017,26(143):160096.
[12] 魏婧韬.高寒低氧环境下旅游人群急性高原病发病率调查[J].社区医学杂志,2017,15(7):22-24.
[13] Bailey DM, Kleger GR, Holzgraefe M, et al. Pathophysiological significance of peroxidative stress, neuronal damage, and membrane permeability in acute mountain sickness[J]. J Appl Physiol, 2004,96(4):1459-1463.
[14] Schmerbach K, Patzak A. Pathophysiological mechanisms in acute mountain sickness[J]. Acta Physiologica, 2013,209(4):246-249.
[15] 薛增军,李英悦.从高原急进特高海拔地区人体血浆内皮素-1水平的变化及其意义[J].高原医学杂志,1997,7(4):23-24.
[16] Liang J, Zhang Z, Liang L, et al. HIF-1a regulated tongue squamous cell carcinoma cell growth via regulating VEGF expression in a xenograft model[J]. Ann Translat Med, 2014, 2(9): 92-98.
[17] Dorward DA, Thompson AA, Baillie JK, et al. Change in plasma vascular endothelial growth factor during onset and recovery from acute mountain sickness[J]. Respirat Med, 2007,101(3):587-594.
[18] 何显菁,廖树森.非对称性二甲基精氨酸与心血管疾病关系的研究进展[J].实用心脑肺血管病杂志,2016,24(3):1-3.
[19] Burtscher M, Brandstatter E, Gatterer H. Preacclimatization insimulated altitudes[J]. Sleep Breath, 2008,12(2):109-114.
[20] 高炜,张世范,赵秋玲,等.急性高原病量化评分系统的前瞻性评估[J].第四军医大学学报,2008,29(2):151-153.