Effect of GBT440 on oxygen-carrying characteristics and its anti-hypoxia effect in hypoxia animal model

Ming WEI; Jian HUANG; Yu CUI; Wenting SU; Xiaoxu LI; Libin GUAN; Yi SHEN

doi:10.16016/j.1000-5404.201911150

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Effect of GBT440 on oxygen-carrying characteristics and its anti-hypoxia effect in hypoxia animal model

Basic Medicine | 更新时间：2026-01-09

- Effect of GBT440 on oxygen-carrying characteristics and its anti-hypoxia effect in hypoxia animal model
- Journal of Third Military Medical University Vol. 42, Issue 9, Pages: 923-928(2020)
- 作者机构：
  
  1.400016 重庆，重庆医科大学：基础医学院干细胞与组织工程研究室病理生理学教研室
  2.400038 重庆，陆军军医大学(第三军医大学):高原军事医学系高原生理学与病理学教研室，全军高原医学重点实验室，特殊环境医学教育部重点实验室
  3.第一附属医院全军病理学研究所
  4.400016 重庆，重庆医科大学：实验教学管理中心
- 作者简介：
- 基金信息：
  
  the Youth Training Plan of Military Medical Science and Technology(20QNPY002);the Key Special Program of "Thirteenth Five-year Plan" of Logistic Scientific Research of PLA(BWS17J031);the Major Project of "Twelfth Five-year Plan" for Logistic Scientific Research of PLA(AWS14L005)
- DOI：10.16016/j.1000-5404.201911150
  CLC： R331.141;R364.4;R965
- Received：18 November 2019，
  
  Revised：2020-02-05，
  
  Published：15 May 2020
- 稿件说明：
移动端阅览
Ming WEI, Jian HUANG, Yu CUI, et al. Effect of GBT440 on oxygen-carrying characteristics and its anti-hypoxia effect in hypoxia animal model[J]. Journal of Third Military Medical University, 2020, 42(9): 923-928.
DOI：

Ming WEI, Jian HUANG, Yu CUI, et al. Effect of GBT440 on oxygen-carrying characteristics and its anti-hypoxia effect in hypoxia animal model[J]. Journal of Third Military Medical University, 2020, 42(9): 923-928. DOI： 10.16016/j.1000-5404.201911150.

摘要

目的

观察血红蛋白变构剂Voxelotor(GBT440)对血液携氧特性的影响及其抗缺氧作用。

方法

将不同浓度GBT440与小鼠全血在37 ℃孵育1 h，通过血氧分析仪绘制氧解离曲线(oxygen dissociation curves

ODCs)并计算P50，且通过分别添加酸、碱改变样本pH值，检测ODCs的变化。将24只SD雄性大鼠按随机数表法分为常氧对照、常氧用药、缺氧对照、缺氧用药组(

=6)。对照组和用药组大鼠分别以0、100 mg/kg GBT440灌胃，1 h后将常氧组和缺氧组大鼠分别置于21%O

和10%O

的密闭小室中；6 h后取所有大鼠腹主动脉血，进行血气检测。另将C57雄性小鼠同以上的分组和实验处理，取材前1.5 h腹腔注射缺氧探针派诺硝唑，用免疫组织化学方法检测小鼠肝、肾、脑组织的缺氧程度。

结果

随着与血液孵育的GBT440浓度的增加，ODCs呈剂量依赖性左移

P50降低(

0.05)，加酸后ODCs右移，加碱后ODCs左移。未使用GBT440时，与常氧组相比，缺氧组动脉氧分压[

)

]

、动脉血氧饱和度(SpO

)均显著降低(

0.05)，肝、肾、脑组织缺氧程度明显加重；使用GBT440后，上述变化得以改善，与缺氧对照组相比，缺氧用药组

)增加了21.35%；SpO

增加了8.14%(

0.05)，肝、肾、脑组织缺氧程度明显减轻。

结论

GBT440能提高血液的携氧能力，改善组织的缺氧程度，有望成为一种有效的抗缺氧药物。

Abstract

Objective

To study the effect of hemoglobin allosteric agent Voxelotor(GBT440) on oxygen-carrying characteristics of blood and its anti-hypoxia effect.

Methods

Whole arterial blood of mice were incubated with different concentrations of GBT440 at 37 ℃ for 1 h

then hemoglobin oxygen dissociation cu

rves(ODCs) were detected by Hemox Analyzer and the P50 was calculated. After the pH value of blood samples changed by adding acid and alkali

the changes of ODCs were detected. SD rats were randomly divided into normoxia control group

normoxia treatment group

hypoxia control group and hypoxia treatment group(

=6). The rats in the control group and the treatment group were given 0 and 100 mg/kg GBT440 respectively by gavage. In 1 h later

the normoxia group and the hypoxia group were respectively placed in closed chambers containing 21% O

and 10%O

and their abdominal aortic blood samples were collected for blood-gas test in another 6 h. The male C57 mice were divided into groups and treated as above. The hypoxyprobe was injected intraperitoneally at 1.5 h before the sampling

and the hypoxia level of the liver

kidney and brain tissues of the mice were detected by immunohistochemistry.

Results

With the increase concentrations of GBT440

ODCs were shifted to the left in a dose-dependent manner and P50 were significantly decreased(

0.05). In the present of GBT440

adding acid induced ODCs right-shift

while adding alkali resulted in it left-shift. In the absence of GBT440

) and SpO

in the hypoxic group were significantly reduced when compared with the normal group(

0.05)

and the hypoxic conditions in the liver

kidney and brain tissues were significantly severer. In the presence of GBT440

these indicators were improved in the hypoxia+GBT440 group than the hypoxia group

) was increased by 21.35% and SpO

by 8.14%(

0.05)

and the hypoxic conditions in above organs were obviously ameliorated.

Conclusion

GBT440 can improve the oxygen carrying capacity of blood and the hypoxic conditions in tissues

and is expected to be an effective anti-hypoxia drug.

关键词

Keywords

references

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Related Author

Wenting SU

Yu CUI

Xiaoxu LI

Libin GUAN

Jian HUANG

Yi SHEN

刘良明

臧家涛

Related Institution

Laboratory of Stem Cell and Tissue Engineering & Department of Pathophysiology, College of Basic Medical Sciences, Chongqing Medical University

Department of High Altitude Physiology and High Altitude Biology, Key Laboratory of Extreme Environmental Medicine of Ministry of Education, Key Laboratory of High Altitude Medicine of PLA, Faculty of High Altitude Military Medicine, Army Medical University (Third Military Medical University)

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