Zhang Jie, Wu Yue, Peng Xiao-Yong, Li Qing-Hui, Xiang Xin-Ming, Zhu Yu, Yan Qing-Guang, Lau Billy, Tzang Feichuen, Liu Liang-Ming, Li Tao
State Key Laboratory of Trauma, Burns and Combined Injury, Department of Shock and Transfusion, Research Institute of Surgery, Daping Hospital, Army Medical University, Chongqing, China.
New Beta Innovation Limited, Kowloon Bay, Hong Kong, SAR China.
Front Physiol. 2021 Sep 27;12:690190. doi: 10.3389/fphys.2021.690190. eCollection 2021.
Hypoxia is the major cause of acute altitude hypoxia injury in acute mountain sickness (AMS). YQ23 is a kind of novel bovine-derived, cross-linked hemoglobin-based oxygen carrier (HBOC). It has an excellent capacity for carrying and releasing oxygen. Whether YQ23 has a protective effect on the acute altitude hypoxia injury in AMS is unclear. In investigating this mechanism, the hypobaric chamber rabbit model and plain-to-plateau goat model were used. Furthermore, this study measured the effects of YQ23 on the ability of general behavior, general vital signs, Electrocardiograph (ECG), hemodynamics, vital organ injury markers, and blood gases in hypobaric chamber rabbits and plain-to-plateau goats. Our results showed that the ability of general behavior (general behavioral scores, GBS) (GBS: 18 ± 0.0 vs. 14 ± 0.5, < 0.01) and the general vital signs weakened [Heart rate (HR, beats/min): 253.5 ± 8.7 vs. 301.1 ± 19.8, < 0.01; Respiratory rate (RR, breaths/min): 86.1 ± 5.2 vs. 101.2 ± 7.2, < 0.01] after exposure to plateau environment. YQ23 treatment significantly improved the ability of general behavior (GBS: 15.8 ± 0.5 vs. 14.0 ± 0.5, < 0.01) and general vital signs [HR (beats/min): 237.8 ± 24.6 vs. 301.1 ± 19.8, < 0.01; RR (breaths/min): 86.9 ± 6.6 vs. 101.2 ± 7.2, < 0.01]. The level of blood PaO2 (mmHg) (115.3 ± 4.7 vs. 64.2 ± 5.6, < 0.01) and SaO2(%) (97.7 ± 0.7 vs. 65.8 ± 3.1, < 0.01) sharply decreased after exposure to plateau, YQ23 treatment significantly improved the blood PaO2 (mmHg) (97.6 ± 3.7 vs. 64.2 ± 5.6, < 0.01) and SaO2(%) (82.7 ± 5.2 vs. 65.8 ± 3.1, < 0.01). The cardiac ischemia and injury marker was increased [troponin (TnT, μg/L):0.08 ± 0.01 vs. 0.12 ± 0.02, < 0.01], as well as the renal [blood urea nitrogen (BUN, mmol/L): 6.0 ± 0.7 vs. 7.3 ± 0.5, < 0.01] and liver injury marker [alanine aminotransferase (ALT, U/L): 45.8 ± 3.6 vs. 54.6 ± 4.2, < 0.01] was increased after exposure to a plateau environment. YQ23 treatment markedly alleviated cardiac ischemia [TnT (μg/L):0.10 ± 0.01 vs 0.12 ± 0.02, < 0.01] and mitigated the vital organ injury. Besides, YQ23 exhibited no adverse effects on hemodynamics, myocardial ischemia, and renal injury. In conclusion, YQ23 effectively alleviates acute altitude hypoxia injury of AMS without aside effects.
低氧是急性高原病（AMS）中急性高原低氧损伤的主要原因。YQ23是一种新型的牛源交联血红蛋白基氧载体（HBOC）。它具有出色的携氧和释氧能力。YQ23对AMS中的急性高原低氧损伤是否具有保护作用尚不清楚。在研究这一机制时，使用了低压舱兔模型和平原至高原山羊模型。此外，本研究测量了YQ23对低压舱兔和平原至高原山羊的一般行为能力、一般生命体征、心电图（ECG）、血流动力学、重要器官损伤标志物和血气的影响。我们的结果表明，暴露于高原环境后，一般行为能力（一般行为评分，GBS）（GBS：18±0.0对14±0.5，P<0.01）和一般生命体征减弱[心率（HR，次/分钟）：253.5±8.7对301.1±19.8，P<0.01；呼吸频率（RR，次/分钟）：86.1±5.2对101.2±7.2，P<0.01]。YQ23治疗显著改善了一般行为能力（GBS：15.8±0.5对14.0±0.5，P<0.01）和一般生命体征[HR（次/分钟）：237.8±24.6对301.1±19.8，P<0.01；RR（次/分钟）：86.9±6.6对101.2±7.2，P<0.01]。暴露于高原后，血液中PaO2（mmHg）水平（115.3±4.7对64.2±5.6，P<0.01）和SaO2（%）（97.7±0.7对65.8±3.1，P<0.01）急剧下降，YQ23治疗显著改善了血液中PaO2（mmHg）（97.6±3.7对64.2±5.6，P<0.01）和SaO2（%）（82.7±5.2对65.8±3.1，P<0.01）。心脏缺血和损伤标志物升高[肌钙蛋白（TnT，μg/L）：0.08±0.01对0.12±0.02，P<0.01]，肾脏[血尿素氮（BUN，mmol/L）：6.0±0.7对7.3±0.5，P<0.01]和肝脏损伤标志物[丙氨酸氨基转移酶（ALT，U/L）：45.8±3.6对54.6±4.2，P<0.01]在暴露于高原环境后也升高。YQ23治疗显著减轻了心脏缺血[TnT（μg/L）：0.10±0.01对0.12±0.02，P<0.01]并减轻了重要器官损伤。此外，YQ23对血流动力学、心肌缺血和肾脏损伤无不良影响。总之YQ23有效减轻AMS的急性高原低氧损伤且无副作用。
