Protective effect and mechanism of RSR13 on lung blast injury in rats at high altitude

Qingying HE; Yue LI; Jing WEN; Lunli XIANG; Jiaxiang DUAN; Xianjian LIAO; Bin YI; Jiaolin NING

doi:10.16016/j.2097-0927.202404091

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Protective effect and mechanism of RSR13 on lung blast injury in rats at high altitude

Military Medicine | 更新时间：2026-01-09

- Protective effect and mechanism of RSR13 on lung blast injury in rats at high altitude
- Journal of Army Medical University Vol. 46, Issue 20, Pages: 2352-2359(2024)
- 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：
- 基金信息：
- DOI：10.16016/j.2097-0927.202404091
  CLC： R730.51;R730.53;R735.2
- Received：18 April 2024，
  
  Revised：2024-06-27，
  
  Published：30 October 2024
- 稿件说明：
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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：

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

references

MACGREGOR A J, ZOURIS J M, WATROUS J R, et al . Multimorbidity a nd quality of life after blast-related injury among US military personnel: a cluster analysis of retrospective data[J ] . BMC Public Health, 2020, 20(1): 578. DOI: 10.1186/s12889-020-08696-4.

KAZMIRCHUK A, YARMOLIUK Y, LURIN I, et al . Ukraine's experience with management of combat casualties using NATO's four-tier "changing as needed" healthcare system[J ] . World J Surg, 2022, 46(12): 2858-2862. DOI: 10.1007/s00268-022-06718-3.

胡方超, 柴家科, 曲毅睿, 等. 乌司他丁对原发性冲击伤小鼠早期肺损伤治疗作用的研究[J]. 解放军医学院学报, 2023, 44(9): 1010-1017. DOI: 10.12435/j.issn.2095-5227.2023.010.

HU F C, CHAI J K, QU Y R, et al . Therapeutical effect of ulinastatin on early lung injury in mice with primary blast injury[J ] . Acad J Chin PLA Med Sch, 2023, 44(9): 1010-1017. DOI: 10.12435/j.issn.2095-5227.2023.010.

王正国. 野战外科学[M]. 北京: 人民卫生出版社, 2010.

WANG Z G. Field surgery[M]. Beijing: People's Medical Publishing House, 2010.

王峰, 杨志焕, 朱佩芳, 等. 高原冲击伤伤情特点的实验研究[J]. 创伤外科杂志, 2008, 10(6): 549-551. DOI: 10.3969/j.issn.1009-4237.2008.06.026.

WANG F, YANG Z H, ZHU P F, et al . Experimental study on characteristics of blast injury at high altitude[J ] . J Trauma Surg, 2008, 10(6): 549-551. DOI: 10.3969/j.issn.1009-4237.2008.06.026.

杨志焕. 高原战创伤的特点及其救治[J]. 创伤外科杂志, 2006, 8(4): 289-292. DOI: 10.3969/j.issn.1009-4237.2006.04.001.

YANG Z H. Characteristics and treatment of war wound and trauma at high altituderegion[J]. J Trauma Surg, 2006, 8 (4): 289-292. DOI: 10.3969/j.issn.1009-4237.2006.04.001.

陈雪梅, 崔欢欢, 郭丽琼, 等. 高原肺冲击伤特点及救治研究进展[J]. 中华灾害救援医学, 2022, 10(1): 26-29. DOI: 10.13919/j.issn.2095-6274.2022.01.006.

CHEN X M, CUI H H, GUO L Q, et al . Research progress on the characteristics and treatment of lung injury caused by high altitude blast[J ] . Chin J Disaster Med, 2022, 10(1): 26-29. DOI: 10.13919/j.issn.2095-6274.2022.01.006.

邓志龙, 杨志焕, 李晓炎, 等. 高压氧、山莨菪碱和地塞米松对高原冲击伤大鼠的治疗作用[J]. 创伤外科杂志, 2012, 14(2): 165-168. DOI: 10.3969/j.issn.1009-4237.2012.02.022.

DENG Z L, YANG Z H, LI X Y, et al . Therapeutic effects of hyperbaric oxygen, anisodaminum and dexamethasome on blast injury in rats exposed to high altitude[J ] . J Trauma Surg, 2012, 14(2): 165-168. DOI: 10.3969/j.issn.1009-4237.2012.02.022.

单佑安, 蒋建新, 杨志焕, 等. 大剂量地塞米松对犬严重肺冲击伤的治疗作用[J]. 第三军医大学学报, 2003, 25(11): 935-937. DOI: 10.3321/j.issn:1000-5404.2003.11.001.

SHAN Y A, JIANG J X, YANG Z H, et al . Effect of high-dose dexamethasone on cani ne severe lung blast injury[J ] . J Third Mil Med Univ, 2003, 25(11): 935-937. DOI: 10.3321/j.issn:1000-5404.2003.11.001.

易云峰. 确立重度肺爆震伤救治中体外膜肺氧合的地位[J]. 创伤外科杂志, 2019, 21(7): 558-561. DOI: 10.3969/j.issn.1009-4237.2019.07.018.

YI Y F. Establishing the role of extracorporeal membrane oxygenation in the treatment of severe pulmonary blastinjury[J]. J Trauma Surg, 2019, 21(7): 558-561. DOI: 10.3969/j.issn.1009-4237.2019.07.018.

HAMELE M, POSS W B, SWENEY J. Disaster preparedness, pediatric considerations in primary blast injury, chemical, and biological terrorism[J]. World J Crit Care Med, 2014, 3(1): 15-23. DOI: 10.5492/wjccm.v3.i1.15.

WEISS R G, MEJIA M A, KASS D A, et al . Preservation of canine myocardial high-energy phosphates during low-flow ischemia with modification of hemoglobin-oxygen affinity[J ] . J Clin Invest, 1999, 103(5): 739-746. DOI: 10.1172/JCI6030.

WATSON J C, DOPPENBERG E M, BULLOCK M R, et al . Effects of the allosteric modification of hemoglobin on brain oxygen and infarct size in a feline model of stroke[J ] . Stroke, 1997, 28(8): 1624-1630. DOI: 10.1161/01.str.28.8.1624.

MENG X Y, LU Q Y, ZHANG J F, et al . A novel animal model of primary blast lung injury and its pathological changes in mice[J ] . J Trauma Acute Care Surg, 2022, 93(4): 530-537. DOI: 10.1097/TA.0000000000003571.

GUY R J, KIRKMAN E, WATKINS P E, et al . Physiologic responses to primary blast[J ] . J Trauma, 1998, 45(6): 983-987. DOI: 10.1097/00005373-199812000-00001.

HOOFD L, BOS C. Extraction pressures calculated for rat heart and dog skeletal muscle and application in models of tissue oxygenation[J]. Adv Exp Med Biol, 1997, 428: 679-685. DOI: 10.1007/978-1-4615-5399-1_95.

BALABAN D Y, DUFFIN J, PREISS D, et al . The in-vivo oxyhaemoglobin dissociation curve at sea level and high altitude[J ] . Respir Physiol Neurobiol, 2013, 186(1): 45-52. DOI: 10.1016/j.resp.2012.12.011..

LIARD J F, KUNERT M P. Hemodynamic changes induced by low blood oxygen affinity in dogs[J]. Am J Physiol, 1993, 264(2 Pt 2): R396-R401. DOI: 10.1152/ajpregu.1993.264.2.R396.

HAN Y M, YOON H, LIM S, et al . Risk factors for vitamin D, zinc, and selenium deficiencies in Korean patients with inflammatory bowel disease[J ] . Gut Liver, 2017, 11(3): 363-369. DOI: 10.5009/gnl16333.

QIU X C, LI H Y, TANG H T, et al . Hydrogen inhalation ameliorates lipopolysaccharide-induced acute lung injury in mice[J ] . Int Immunopharmacol, 2011, 11(12): 2130-2137. DOI: 10.1016/j.intimp.2011.09.007.

YANG J, WANG Y, LIU H, et al . C2-ceramide influences alveolar epithelial barrier function by downregulating Zo-1, occludin and claudin-4 expression[J ] . Toxicol Mech Methods, 2017, 27(4): 293-297. DOI: 10.1080/15376516.2017.1278812.

FURUSE M, HIRASE T, ITOH M, et al . Occludin: a novel integral membrane protein localizing at tight junctions[J ] . J Cell Biol, 1993, 123(6 Pt 2): 1777-1788. DOI: 10.1083/jcb.123.6.1777.

CONG P F, TONG C C, MAO S, et al . DDAH1 promotes lung endothelial barrier repair by decreasing leukocyte transendothelial migration and oxidative stress in explosion-induced lung injury[J ] . Oxid Med Cell Longev, 2022, 2022: 8407635. DOI: 10.1155/2022/8407635.

LIU B H, ZHANG J, SUN P, et al . Raw bowl tea (Tuocha) polyphenol prevention of nonalcoholic fatty liver disease by regulating intestinal function in mice[J ] . Biomolecules, 2019, 9(9): 435. DOI: 10.3390/biom9090435.

LOSSI L, CASTAGNA C, MERIGHI A. Caspase-3 mediated cell death in the normal development of the mammalian cerebellum[J]. Int J Mol Sci, 2018, 19(12): 3999. DOI: 10.3390/ijms19123999.

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