Bennetts Paul, Shen Qiuhua, Thimmesch Amanda R, Diaz Francisco J, Clancy Richard L, Pierce Janet D
Department of Nurse Anesthesia Education, University of Kansas, Kansas City, KS, 66160, USA.
School of Nursing, University of Kansas, Kansas City, KS, 66160, USA
Exp Physiol. 2014 Jul;99(7):1007-15. doi: 10.1113/expphysiol.2014.078600. Epub 2014 May 23.
Haemorrhagic shock (HS) and fluid resuscitation can lead to increased reactive oxygen species (ROS), contributing to ischaemia-reperfusion injury and organ damage. Ubiquinol is a potent antioxidant that decreases ROS. This study examined the effects of ubiquinol administered with fluid resuscitation following controlled HS. Adult male Sprague-Dawley rats were randomly assigned to treatment [ubiquinol, 1 mg (100 g body weight)(-1)] or control groups. Rats were subjected to 60 min of HS by removing 40% of the total blood volume to a mean arterial pressure ∼45-55 mmHg. The animals were resuscitated with blood and lactated Ringer solution, with or without ubiquinol, and monitored for 120 min. At the end of the experiments, the rats were killed and the lungs, diaphragm, heart and kidneys harvested. Leucocytes were analysed for mitochondrial superoxide at baseline, end of shock and 120 min following fluid resuscitation using MitoSOX Red. Diaphragms were examined for hydrogen peroxide using dihydrofluorescein diacetate and confocal microscopy. The apoptosis in lungs, diaphragm, heart and kidneys was measured using fluorescence microscopy with acridine orange and ethidium bromide. Leucocyte mitochondrial superoxide levels were significantly lower in rats that received ubiquinol than in the control animals. Production of hydrogen peroxide and apoptosis were significantly reduced in the organs of rats treated with ubiquinol. These findings suggest that ubiquinol, administered with fluid resuscitation after HS, attenuates ROS production and apoptosis. Thus, ubiquinol is a potent antioxidant that may be used as a potential treatment to reduce organ injury following haemorrhagic events.
失血性休克（HS）和液体复苏可导致活性氧（ROS）增加，进而引发缺血再灌注损伤和器官损害。泛醇是一种有效的抗氧化剂，可降低ROS水平。本研究检测了在控制性HS后进行液体复苏时给予泛醇的效果。成年雄性Sprague-Dawley大鼠被随机分为治疗组[泛醇，1mg/（100g体重）⁻¹]或对照组。通过抽取40%的总血容量使大鼠平均动脉压降至约45 - 55mmHg，造成HS 60分钟。动物用血液和乳酸林格液进行复苏，复苏时或添加或不添加泛醇，并监测120分钟。实验结束时，处死大鼠，摘取肺、膈肌、心脏和肾脏。使用MitoSOX Red分析白细胞在基线、休克结束时以及液体复苏后120分钟时的线粒体超氧化物水平。使用二氢荧光素二乙酸酯和共聚焦显微镜检测膈肌中的过氧化氢。使用吖啶橙和溴化乙锭荧光显微镜检测肺、膈肌、心脏和肾脏中的细胞凋亡情况。接受泛醇治疗的大鼠白细胞线粒体超氧化物水平显著低于对照动物。泛醇治疗的大鼠器官中过氧化氢的产生和细胞凋亡均显著减少。这些发现表明，HS后液体复苏时给予泛醇可减轻ROS产生和细胞凋亡。因此，泛醇是一种有效的抗氧化剂，可作为减少出血事件后器官损伤的潜在治疗药物。
