HOE-642 improves the protection of hypothermia on neuronal mitochondria after cardiac arrest in rats
HOE-642 improves the protection of hypothermia on neuronal mitochondria after cardiac arrest in rats
复制标题
HOE-642改善大鼠心脏骤停后神经元线粒体的低温保护
DOI：
--
复制
发表时间：
2020
影响因子：
2.2
通讯作者：
Fei Han
中科院分区：
文献类型：
--
作者：
Lanying Wei;Pengjiao Zhang;Yanan Hu;Wenshuai Zhao;Xintong Liu;Xifan Wang;Fei Han
摘要：HOE-642已被证明在多种脑和心肌缺血/再灌注损伤模型中具有显著的保护作用。在这项研究中，我们研究了选择性Na+/H+交换1抑制剂HOE-642在复苏过程中对神经元和神经元线粒体功能的影响。大鼠窒息8min后心跳骤停。实验分为5组：假手术组、常温组(N)、HOE-642组(HOE，1 mg/kg)、亚低温组(Hypo，33±0.5℃)、HOE-642+亚低温组(HOE+Hypo)。复苏后24 h进行存活评分和神经功能缺失评分。观察脑组织线粒体ΔΨm、线粒体肿胀、ROS生成、线粒体复合体I-IV活性及超微结构变化。HOE+Hypo组存活率(85.7%)高于N组(42.9%)和HOE组(31.8%)，P<0.05。Hypo组和HoE+Hypo组的NDS均低于N组和HoE组，P<0.05。HOE组ΔΨm(2.7±0.9)高于N组(1.3±0.3)和Hypo组(1.4±0.4)，P<0.0 5。N组线粒体肿胀较HOE组和Hypo组严重，P<；0.05。HOE组和HOE+Hypo组的ROS产生均低于N组，P<0.05。HOE+Hypo组的复合体I-IV活性高于其他组。N组线粒体超微结构严重受损。HOE组、Hypo组和HOE+Hypo组线粒体结构保持完整。复苏过程中HOE-642加低温较单纯HOE-642或单纯低温更有利。
Abstract: HOE-642 has been shown to provide significant protection in a variety of models of cerebral and myocardial ischemia/reperfusion injury. In this study, we examined the impact of HOE-642, a selective Na+/H+ exchanger 1 inhibitor, with or without hypothermia on neuronal and neuronal mitochondrial function during resuscitation. Cardiac arrest was induced by 8 min of asphyxia in rats. Five groups were included in this study: sham; normothermia (N); HOE-642 (HOE, 1 mg/kg); hypothermia (Hypo, 33±0.5°C); and HOE-642 plus hypothermia (HOE+Hypo). Survival and neurological deficit scores (NDS) were evaluated after 24 h of resuscitation. ΔΨm, mitochondrial swelling, ROS production, mitochondrial complex I-IV activity, and ultrastructural changes of the hippocampal mitochondria were evaluated. Survival in the HOE+Hypo group (85.7%) was higher than in the N group (42.9%) and HOE group (31.8%), P<0.05. NDS in the Hypo and HOE+Hypo groups were lower than in the N and HOE groups, P<0.05. ΔΨm in the HOE group (2.7±0.9) were higher than in the N (1.3±0.3) and Hypo (1.4±0.4) groups, P<0.05. Mitochondrial swelling in the N group was severe than in the HOE and Hypo groups, P<0.05. The production of ROS in the HOE and HOE+Hypo groups were lower than in the N group, P<0.05. Complex I-IV activity in the HOE+Hypo group was higher than in the other groups. The ultrastructure of mitochondria in the N group was severely damaged. The mitochondria maintained structural integrity in the HOE, Hypo and HOE+Hypo groups. HOE-642 plus hypothermia during resuscitation was beneficial than HOE-642 or hypothermia alone.