RSR13对高原大鼠肺冲击伤的保护作用及机制研究

何青盈; 李悦; 文静; 向伦理; 段家翔; 廖先建; 易斌; 甯交琳

doi:10.16016/j.2097-0927.202404091

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RSR13对高原大鼠肺冲击伤的保护作用及机制研究

军事医学 | 更新时间：2026-01-09

- RSR13对高原大鼠肺冲击伤的保护作用及机制研究
- Protective effect and mechanism of RSR13 on lung blast injury in rats at high altitude
- 陆军军医大学学报 2024年46卷第20期页码：2352-2359
- 作者机构：
  
  1.400038 重庆，陆军军医大学(第三军医大学)第一附属医院麻醉科
  2.400038 重庆，陆军军医大学(第三军医大学)第一附属医院肾内科
- 作者简介：
  
  [甯交琳，E-mail：ningjiaolin@tmmu.edu.cn NING Jiaolin, E-mail: ningjiaolin@tmmu.edu.cn
- 基金信息：
- DOI：10.16016/j.2097-0927.202404091
  中图分类号： R730.51;R730.53;R735.2
- 收稿：2024-04-18，
  
  修回：2024-06-27，
  
  纸质出版：2024-10-30
- 稿件说明：
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何青盈, 李悦, 文静, 等. RSR13对高原大鼠肺冲击伤的保护作用及机制研究[J]. 陆军军医大学学报, 2024,46(20):2352-2359.

Qingying HE, Yue LI, Jing WEN, et al. Protective effect and mechanism of RSR13 on lung blast injury in rats at high altitude[J]. Journal of Army Medical University, 2024, 46(20): 2352-2359.
何青盈, 李悦, 文静, 等. RSR13对高原大鼠肺冲击伤的保护作用及机制研究[J]. 陆军军医大学学报, 2024,46(20):2352-2359. DOI： 10.16016/j.2097-0927.202404091.

Qingying HE, Yue LI, Jing WEN, et al. Protective effect and mechanism of RSR13 on lung blast injury in rats at high altitude[J]. Journal of Army Medical University, 2024, 46(20): 2352-2359. DOI： 10.16016/j.2097-0927.202404091.

摘要

目的

探究血红蛋白变构剂乙丙昔罗[efaproxiral(RSR13)]对高原地区爆炸冲击波致大鼠肺损伤的影响及其作用机制。

方法

8周龄SD健康雄性大鼠，共82只，按照随机数字表法分为冲击伤组和RSR13+冲击伤组，RSR13+冲击伤组大鼠在接受冲击前2 h腹腔注射RSR13(150 mg/kg)：其中60只大鼠放置在距爆源同侧5 m处，为5 m冲击伤组(

=30)、5 m RSR13+冲击伤组(

=30)；16只大鼠放置在距爆源同侧6 m处，6 m冲击伤组(

=8)、6 m RSR13+冲击伤组(

=8)，余下6只大鼠为对照组(

=6)。观察距爆源5 m处各组大鼠24 h内生存情况。对距爆源6 m处存活24 h大鼠，采用HE染色与肺损伤病理评分比较各组大鼠肺组织损伤情况，测定大鼠动脉血气；采用比色法检测肺组织谷胱甘肽(glutathione，GSH)、丙二醛(malondialdehyde，MDA)、超氧化物歧化酶(superoxide dismutase，SOD)水平；通过蛋白免疫印迹法检测肺组织中剪切胱天蛋白酶-3(cleaved caspase-3)、闭合蛋白(occludin)的表达水平。

结果

RSR13预处理可增加高原环境下距爆源5 m处爆炸后即刻存活率[46.7%(冲击伤组)

93.3%(RSR13+冲击伤组)，

＜0.01

]

和爆炸后1 h存活率[46.7%(冲击伤组)

86.7%(RSR13+冲击伤组)，

＜0.01

]

。RSR13可降低高原环境下距爆源6 m处大鼠肺损伤病理评分[(13.70±0.78)(冲击伤组)

(8.27±0.93)(RSR13+冲击伤组)，

＜0.01

]

。RSR13对高原环境下肺冲击伤大鼠动脉血气无明显影响(

0.05)，RSR13可增加高原距爆源6 m处大鼠肺组织GSH含量[(22.62±10.88)(冲击伤组)

(40.27±12.47)(RSR13+冲击伤组)μg/g，

＜0.05)、但对MDA含量与SOD活性无明显影响(

0.05)，降低肺组织cleaved caspase-3表达量(

＜0.01)、增加occludin表达量(

＜0.05)。

结论

RSR13对高原爆炸冲击波所致大鼠肺损伤具有显著的保护作用，这可能与其增加组织抗氧化能力，减少细胞凋亡和降低肺通气屏障通透性有关。

Abstract

Objective

To investigate the impact and mechanism of efaproxiral (RSR13)

a hemoglobin allosteric agent

on lung injury in rats caused by explosion-induced shock waves in plateau areas.

Methods

Eighty-two healthy male SD rats (8-week-old

transferred from an altitude of 2 880 m to 4 700 m within 6 h) were randomly divided into blast injury group and RSR13+blast injury group (intraperitoneal i

njection of 150 mg/kg RSR13 2 h before explosion). Sixty rats were positioned at 5 m from the explosion source and divided into 5-m blast injury group (

=30) and 5-m RSR13+blast injury group (

=30). Additionally

16 rats were positioned at 6 m from the explosion source and then assigned into 6-m blast injury group (

=8) and 6-m RSR13+blast injury group (

=8). The left 6 rats served as control (

=6). Survival outcomes of each rat group positioned 5 m from the explosion source were observed over a 24-hour period. HE staining was used to evaluate the pathological score of the surviving rats positioned at 6 m from the explosion source in 24 h after explosion

along with arterial blood gas analysis. The contents of glutathione (GSH)

malondialdehyde (MDA) and superoxide dismutase (SOD) in the lung tissues were determined by colorimetry. Western blotting was conducted to measure the expression levels of cleaved caspase-3 and occludin in the lung tissue.

Results

RSR13 pretreatment increased the survival rate immediately after explosion (93.3%

46.7%

0.01) and at 1 h after explosion (86.7%

46.7%

0.01) in plateau areas of 5 m from the explosion source. At high altitude

RSR13 pretreatment reduced the pathological score of lung injury in rats 6 m away from the explosion source (8.27±0.93

13.70±0.78

0.01)

but had no significant effect on the results of arterial blood gas analysis in rats with lung blast injury (

0.05). In addition

RSR13 pretreatment also increased GSH content (40.27±12.47

22.62±10.88 μg/g

0.05)

but showed no obvious effect on MDA content and SOD activity (

0.05)

decreased the protein level of cleaved caspase-3 (

0.01) and increased that of occlu

din (

0.05) in the lung tissues.

Conclusion

RSR13 exerts significant protective effect on lung injury in rats caused by explosion-induced shock waves in high-altitude environment

which may be related to its increasing antioxidant capacity

reducing cell apoptosis and decreasing barrier permeability of lung ventilation.

关键词

Keywords

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