Gao Yunan, Yang Hongxiao, Chi Jing, Xu Qiannan, Zhao Luqi, Yang Weijia, Liu Weifan, Yang Wei
Department of Cardiology, the Fourth Affiliated Hospital of Harbin Medical University, Harbin, China.
Department of Cardiology, the First Affiliated Hospital of Harbin Medical University, Harbin, China.
Cell Physiol Biochem. 2017;43(4):1503-1514. doi: 10.1159/000481974. Epub 2017 Oct 16.
BACKGROUND/AIMS: To study the effect of inhaling hydrogen gas on myocardial ischemic/reperfusion(I/R) injury in rats.
Seventy male Wistar albino rats were divided into five groups at random as the sham group (Sham). The I/R group (I/R), The ischemic postconditioning group (IPo), The I/R plus hydrogen group (IH2) and the ischemic postconditioning plus hydrogen group (IPoH2). The Sham group was without coronary occlusion. In I/R group, Ischemic/reperfusion injury was induced by coronary occlusion for 1 hour. Followed by 2 hours of reperfusion. In the IPo and IPoH2 group, four cycles of 1 min reperfusion/1 min ischemia was given at the end of 1 hour coronary occlusion. While 2% hydrogen was administered by inhalation 5 min before reperfusion till 2 hours after reperfusion in both the IPoH2 and IH2 group. The heart and blood samples were harvested at the end of the surgical protocol. Then the myocardium cell endoplasmic reticulum(ER) stress and autophagy was observed by electron microscope. In addition, the cardiac ER stress and autophagy related proteins expression were detected by Western blotting analysis.
Both inhaling 2% hydrogen and ischemic postconditioning treatment reduced the ischemic size and serum troponin I level in rats with I/R injury, and inhaling hydrogen showed a more curative effect compared with ischemic postconditioning treatment. Meanwhile inhaling hydrogen showed a better protective effect in attenuating tissue reactive oxygen species. Malondialdehyde levels and immunoreactivities against 8-hydroxy-2'-deoxyguanosine and inhibiting cardiac endoplasmic reticulum stress and down-regulating autophagy as compared with ischemic postconditioning treatment.
These results revealed a better protective effect of hydrogen on myocardial ischemic/reperfusion injury in rats by attenuating endoplasmic reticulum stress and down-regulating autophagy compared with ischemic postconditioning treatment.
背景/目的:研究吸入氢气对大鼠心肌缺血/再灌注(I/R)损伤的影响。
将70只雄性Wistar白化大鼠随机分为五组,即假手术组(Sham)、I/R组(I/R)、缺血后处理组(IPo)、I/R加氢气组(IH2)和缺血后处理加氢气组(IPoH2)。假手术组不进行冠状动脉闭塞。I/R组通过冠状动脉闭塞1小时诱导缺血/再灌注损伤,随后再灌注2小时。IPo组和IPoH2组在冠状动脉闭塞1小时结束时给予4个周期的1分钟再灌注/1分钟缺血。而IPoH2组和IH2组在再灌注前5分钟开始吸入2%氢气,直至再灌注后2小时。手术结束时采集心脏和血液样本。然后通过电子显微镜观察心肌细胞内质网(ER)应激和自噬情况。此外,通过蛋白质免疫印迹分析检测心脏ER应激和自噬相关蛋白的表达。
吸入2%氢气和缺血后处理均能减小I/R损伤大鼠的缺血面积和降低血清肌钙蛋白I水平,且吸入氢气的疗效优于缺血后处理。同时,与缺血后处理相比,吸入氢气在减轻组织活性氧、丙二醛水平以及8-羟基-2'-脱氧鸟苷免疫反应性方面具有更好的保护作用,还能抑制心脏内质网应激并下调自噬。
这些结果表明,与缺血后处理相比,氢气通过减轻内质网应激和下调自噬对大鼠心肌缺血/再灌注损伤具有更好的保护作用。