Chi Jing, Li Zizhuo, Hong Xiaojian, Zhao Tong, Bie Yueyue, Zhang Wen, Yang Jiaxing, Feng Ziming, Yu Zhouqi, Xu Qiannan, Zhao Luqi, Liu Weifan, Gao Yunan, Yang Hongxiao, Yang Jiemei, Liu Jiaren, Yang Wei
Department of Cardiology, The First Affiliated Hospital of Harbin Medical University, Harbin, China.
Department of Abdominal Ultrasonography, The First Affiliated Hospital of Harbin Medical University, Harbin, China.
Front Physiol. 2018 Jul 31;9:1026. doi: 10.3389/fphys.2018.01026. eCollection 2018.
Continuous damage from oxidative stress and apoptosis are the important mechanisms that facilitate chronic heart failure (CHF). Molecular hydrogen (H) has potentiality in the aspects of anti-oxidation. The objectives of this study were to investigate the possible mechanism of H inhalation in delaying the progress of CHF. A total of 60 Sprague-Dawley (SD) rats were randomly divided into four groups: Sham, Sham treated with H, CHF and CHF treated with H. Rats from CHF and CHF treated with H groups were injected isoprenaline subcutaneously to establish the rat CHF model. One month later, the rat with CHF was identified by the echocardiography. After inhalation of H, cardiac function was improved vs. CHF ( < 0.05), whereas oxidative stress damage and apoptosis were significantly attenuated ( < 0.05). In this study, the mild oxidative stress was induced in primary cardiomyocytes of rats, and H treatments significantly reduced oxidative stress damage and apoptosis in cardiomyocytes ( < 0.05 or < 0.01). Finally, as a pivotal transcription factor in reactive oxygen species (ROS)-apoptosis signaling pathway, the expression and phosphorylation of p53 were significantly reduced by H treatment in this rat model and H9c2 cells ( < 0.05 or < 0.01). As a safe antioxidant, molecular hydrogen mitigates the progression of CHF via inhibiting apoptosis modulated by p53. Therefore, from the translational point of view and speculation, H is equipped with potential therapeutic application as a novel antioxidant in protecting CHF in the future.
氧化应激和细胞凋亡造成的持续性损伤是促使慢性心力衰竭（CHF）发生发展的重要机制。分子氢（H₂）在抗氧化方面具有潜在作用。本研究旨在探讨吸入氢气延缓慢性心力衰竭进展的可能机制。将60只Sprague-Dawley（SD）大鼠随机分为四组：假手术组、氢气处理假手术组、慢性心力衰竭组和氢气处理慢性心力衰竭组。慢性心力衰竭组和氢气处理慢性心力衰竭组大鼠皮下注射异丙肾上腺素以建立大鼠慢性心力衰竭模型。1个月后，通过超声心动图鉴定慢性心力衰竭大鼠。吸入氢气后，与慢性心力衰竭组相比，心功能得到改善（P<0.05），而氧化应激损伤和细胞凋亡明显减轻（P<0.05）。本研究在大鼠原代心肌细胞中诱导轻度氧化应激，氢气处理显著降低了心肌细胞的氧化应激损伤和细胞凋亡（P<0.05或P<0.01）。最后，作为活性氧（ROS）-细胞凋亡信号通路中的关键转录因子，在该大鼠模型和H9c2细胞中，氢气处理显著降低了p53的表达和磷酸化水平（P<0.05或P<0.01）。作为一种安全的抗氧化剂，分子氢通过抑制p53介导的细胞凋亡来减轻慢性心力衰竭的进展。因此，从转化医学角度推测，氢气作为一种新型抗氧化剂在未来保护慢性心力衰竭方面具有潜在的治疗应用价值。
