Carbon Monoxide-Saturated Hemoglobin-Based Oxygen Carriers Attenuate High-Altitude-Induced Cardiac Injury by Amelioration of the Inflammation Response and Mitochondrial Oxidative Damage
Carbon Monoxide-Saturated Hemoglobin-Based Oxygen Carriers Attenuate High-Altitude-Induced Cardiac Injury by Amelioration of the Inflammation Response and Mitochondrial Oxidative Damage
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DOI：
10.1159/000448652
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发表时间：
2016-10
期刊：
影响因子：
1.9
通讯作者：
Qingshu Wang;Ling Hu;Yu Hu;G. Gong;Hua Tan;Liling Deng;Xiaoqin Sun;Xiaobo Yi;Yangyang Sun;Wei Wu;Tao Li
中科院分区：
文献类型：
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作者：
Qingshu Wang;Ling Hu;Yu Hu;G. Gong;Hua Tan;Liling Deng;Xiaoqin Sun;Xiaobo Yi;Yangyang Sun;Wei Wu;Tao Li
目的：探讨一氧化碳（CO）对高原缺氧所致心脏损伤的治疗作用。方法：40只雄性C57BL/6小鼠随机分为4组。小鼠在低压室中暴露于常氧或模拟5500米高海拔缺氧环境7天。在前3天内，小鼠以0.3 g Hb/kg/天的剂量或等体积的盐水预处理CO饱和血红蛋白(Hb)基氧载体(CO-HBOC)、氧饱和血红蛋白基氧载体(O2-HBOC)。还测量了体内左心室功能、心肌酶释放、组织病理学变化、细胞凋亡和炎症。结果：高原缺氧会导致严重的心脏损伤，心脏功能受损以及促凋亡、促炎症和促氧化标记物增加就证明了这一点。 CO-HBOC 预处理显着改善心脏功能，减少心肌酶释放并限制心肌细胞凋亡。增加的炎症反应也受到抑制。除了保留线粒体结构外，低压缺氧引起的线粒体氧化损伤也显着减弱。此外，这些抗凋亡和抗氧化作用还伴随着 Akt、ERK 和 STAT3 磷酸化的上调。结论：本研究表明，CO-HBOC 对高原缺氧引起的心肌损伤具有良好的保护作用，该作用是通过抑制炎症和线粒体氧化损伤介导的。
Objective: To investigate the therapeutic effect of carbon monoxide (CO) on high-altitude hypoxia-induced cardiac damage. Methods: Forty male C57BL/6 mice were randomly divided into 4 groups. The mice were exposed to normoxia or simulated 5,500-meter high-altitude hypoxia in a hypobaric chamber for 7 days. During the first 3 days, the mice were pretreated with CO-saturated hemoglobin (Hb)-based oxygen carrier (CO-HBOC), oxygen-saturated hemoglobin-based oxygen carrier (O2-HBOC) at a dose of 0.3 g Hb/kg/day or an equivalent volume of saline. The in vivo left ventricle function, cardiac enzyme release, histopathological changes, apoptosis and inflammation were also measured. Results: High-altitude hypoxia induced significant cardiac damage, as demonstrated by impaired cardiac function and increased proapoptotic, proinflammatory and pro-oxidant markers. Pretreatment with CO-HBOC significantly improved cardiac performance, reduced cardiac enzyme release and limited myocardial apoptosis. The increased inflammatory response was also suppressed. In addition to the preserved mitochondrial structure, hypobaric hypoxia-induced mitochondrial oxidative damage was remarkably attenuated. Moreover, these antiapoptotic and antioxidative effects were accompanied by an upregulated phosphorylation of Akt, ERK and STAT3. Conclusion: This study demonstrated that CO-HBOC provides a promising protective effect on high-altitude hypoxia-induced myocardial injury, which is mediated by the inhibition of inflammation and mitochondrial oxidative damage.