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浙江大学学报（医学版）
浙江大学学报（医学版）  2019, Vol. 48 Issue (6): 674-681    DOI: 10.3785/j.issn.1008-9292.2019.12.13
综述     
血红蛋白在高原低氧适应中的机制研究进展
李雪1,2(),李文斌2(),封士兰1,*(),王荣1,2,*()
1. 兰州大学药学院, 甘肃 兰州 730000
2. 解放军联勤保障部队第九四○医院全军高原医学重点实验室, 甘肃 兰州 730050
Research progress on mechanism in adaptation of hemoglobin to plateau hypoxia
LI Xue1,2(),LI Wenbin2(),FENG Shilan1,*(),WANG Rong1,2,*()
1. School of Pharmacy, Lanzhou University, Lanzhou 730000, China
2. Key Laboratory of the Plateau Medicine, the 940 th Hospital of PLA Joint Logistics Support Force, Lanzhou 730050, China
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摘要：

低氧分压是造成急性高山病的主要原因。机体中血红蛋白在氧的结合、利用、运输、释放中起着重要作用，增加血红蛋白的氧气结合量或者在组织中的供氧量有助于缓解高原病。但增加血红蛋白含量有一定的局限性，研究人员利用分子生物学的技术，寻找可调节血红蛋白构象的内源性或外源性物质，提高肺泡中的摄氧量或肺泡氧在组织中的利用率。目前有关变构调节剂改善血红蛋白亲和力的研究已取得一定进展，将这一机制运用到高原低氧的研究也正在展开。本文从血红蛋白与高原低氧的关系入手，阐述了血红蛋白的结构以及各种变构调节剂在低氧中发挥的作用，希望为寻找新的调节血红蛋白构象的物质提供理论依据。
关键词： 血红蛋白类;  高海拔;  高原病;  低氧/病理生理学;  适应, 生理学;  别构调节;  综述    
Abstract:

Low oxygen partial pressure is the main cause of acute mountain sickness.Hemoglobin plays a crucial physiological role in the binding, utilization, transportation and release of oxygen in the body. To increase the capacity of oxygen binding of hemoglobin or the capacity of oxygen supply in tissues can help alleviate altitude sickness. However, increasing hemoglobin content has certain limitations. Using techniques from molecular biology, researchers are looking for endogenous or exogenous substances that can regulate the conformation of hemoglobin to increase oxygen uptake in the alveoli, or the availability of alveolar oxygen in the tissues. At present, the research on allosteric modulators to improve the affinity of hemoglobin has made some progress, and research on applying this mechanism to plateau hypoxia is also underway. This article reviews the relationship between hemoglobin and hypoxia, the structure of hemoglobin and the role of various allosteric modulators in hypoxia, which would provide information for finding new substances regulating the conformation of hemoglobin.
Key words: Hemoglobins    Altitude    Altitude sickness    Hypoxia/physiopathology    Adaptation, physiological    Allosteric regulation    Review
收稿日期: 2019-10-15 出版日期: 2020-01-19
:  R594.3  
基金资助: 国家自然科学基金(81673508)
通讯作者: 封士兰,王荣     E-mail: lixue18@lzu.edu.cn;yfcs2002@163.com;fengshl@lzu.edu.cn;wangrong-69@163.com
作者简介: 李雪(1997-), 女, 硕士研究生, 主要从事高原药物抗缺氧研究; E-mail:lixue18@lzu.edu.cn; https://orcid.org/0000-0001-8461-367X|李文斌(1982-), 男, 博士, 副主任药师, 主要从事高原药代动力学等研究; E-mail:yfcs2002@163.com; https://orcid.org/0000-0002-8064-269X
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引用本文:

李雪,李文斌,封士兰,王荣. 血红蛋白在高原低氧适应中的机制研究进展[J]. 浙江大学学报（医学版）, 2019, 48(6): 674-681.

LI Xue,LI Wenbin,FENG Shilan,WANG Rong. Research progress on mechanism in adaptation of hemoglobin to plateau hypoxia. J Zhejiang Univ (Med Sci), 2019, 48(6): 674-681.

链接本文:

http://www.zjujournals.com/med/CN/10.3785/j.issn.1008-9292.2019.12.13    或    http://www.zjujournals.com/med/CN/Y2019/V48/I6/674

指标 平原移居者 高原世居者
藏族人 埃塞俄比亚人 安第斯人
血红蛋白 增加 较低 同0海拔处 随年龄增长而增加，与海拔相关
血氧饱和度 随海拔升高而降低 较低 同0海拔处 较低
通气量 增加 高静息通气量 高于0海拔处 低静息通气量
表 1  平原移居者与高原世居者的血氧指标分析
图 1  去氧血红蛋白和氧合血红蛋白的空间结构
图 2  组织红细胞中血红蛋白释放氧示意图
图 3  人血红蛋白的2, 3-二磷酸甘油酸结合位点示意图
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