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Combination therapy of normobaric oxygen with hypothermia or ethanol modulates pyruvate dehydrogenase complex in thromboembolic cerebral ischemia.
Journal of Neuroscience Research ( IF 2.9 ) Pub Date : 2016-03-31 , DOI: 10.1002/jnr.23740
Lipeng Cai 1, 2, 3 , Alexa Thibodeau 2 , Changya Peng 2 , Xunming Ji 1 , Radhika Rastogi 2 , Ruiqiang Xin 2, 4 , Sunpreet Singh 2 , Xiaokun Geng 1, 2, 3 , Jose A Rafols 5 , Yuchuan Ding 1, 2
Journal of Neuroscience Research ( IF 2.9 ) Pub Date : 2016-03-31 , DOI: 10.1002/jnr.23740
Lipeng Cai 1, 2, 3 , Alexa Thibodeau 2 , Changya Peng 2 , Xunming Ji 1 , Radhika Rastogi 2 , Ruiqiang Xin 2, 4 , Sunpreet Singh 2 , Xiaokun Geng 1, 2, 3 , Jose A Rafols 5 , Yuchuan Ding 1, 2
Affiliation
Pyruvate dehydrogenase complex (PDH) is a brain mitochondrial matrix enzyme. PDH impairment after stroke is particularly devastating given PDH's critical role in the link between anaerobic and aerobic metabolism. This study evaluates the restoration of oxidative metabolism and energy regulation with a therapeutic combination of normobaric oxygen (NBO) plus either therapeutic hypothermia (TH) or ethanol. Sprague-Dawley rats were subjected to middle cerebral artery occlusion with an autologous embolus. One hour after occlusion, tissue-type plasminogen activator (t-PA) was administered alone or with NBO (60%), EtOH (1.0 g/kg), or TH (33°C), either singly or in combination. Neurological deficit score and infarct volume were assessed 24 hr after t-PA-induced reperfusion. PDH activity and reactive oxygen species (ROS) levels were measured 3 and 24 hr after t-PA. Western blotting was used to detect PDH and pyruvate dehydrogenase kinase (PDK) protein expression. After t-PA in ischemic rats, NBO combined with TH or EtOH most effectively decreased infarct volume and neurological deficit. The combined therapies produced greater increases in PDH activity and protein expression as well as greater decreases in PDK expression. Compared with the monotherapeutic approaches, the combined therapies provided the most significant declines in ROS generation. Reperfusion with t-PA followed by 60% NBO improves the efficacy of EtOH or TH in neuroprotection by ameliorating oxidative injury and improving PDH regulation. Comparable neuroprotective effects were found when treating with either EtOH or TH, suggesting a similar mechanism of neuroprotection and the possibility of substituting EtOH for TH in clinical settings. © 2016 Wiley Periodicals, Inc.
中文翻译:
正常氧与体温过低或乙醇的联合治疗可调节血栓栓塞性脑缺血中的丙酮酸脱氢酶复合物。
丙酮酸脱氢酶复合物(PDH)是一种脑线粒体基质酶。鉴于PDH在厌氧和有氧代谢之间的联系中起着至关重要的作用,因此中风后PDH的损害尤其具有破坏性。这项研究评估了常压氧气(NBO)加上低温治疗(TH)或乙醇的治疗组合对氧化代谢和能量调节的恢复。Sprague-Dawley大鼠用自体栓塞进行大脑中动脉闭塞。闭塞后一小时,单独或与NBO(60%),EtOH(1.0 g / kg)或TH(33°C)一起单独或与组织型纤溶酶原激活剂(t-PA)一起给药。在t-PA诱导的再灌注后24小时评估神经功能缺损评分和梗塞体积。在t-PA后3和24小时测量PDH活性和活性氧(ROS)水平。Western印迹用于检测PDH和丙酮酸脱氢酶激酶(PDK)蛋白表达。在缺血大鼠中进行t-PA后,NBO联合TH或EtOH最有效地减少了梗塞体积和神经功能缺损。组合疗法使PDH活性和蛋白质表达增加更多,以及PDK表达减少更多。与单一疗法相比,联合疗法在ROS产生方面的降幅最大。用t-PA再加上60%NBO再灌注可改善氧化损伤并改善PDH调节,从而改善EtOH或TH在神经保护中的功效。当用EtOH或TH进行治疗时,发现具有类似的神经保护作用,提示了类似的神经保护机制以及在临床环境中用EtOH替代TH的可能性。©2016 Wiley Periodicals,Inc.
更新日期:2019-11-01
中文翻译:
![](https://scdn.x-mol.com/jcss/images/paperTranslation.png)
正常氧与体温过低或乙醇的联合治疗可调节血栓栓塞性脑缺血中的丙酮酸脱氢酶复合物。
丙酮酸脱氢酶复合物(PDH)是一种脑线粒体基质酶。鉴于PDH在厌氧和有氧代谢之间的联系中起着至关重要的作用,因此中风后PDH的损害尤其具有破坏性。这项研究评估了常压氧气(NBO)加上低温治疗(TH)或乙醇的治疗组合对氧化代谢和能量调节的恢复。Sprague-Dawley大鼠用自体栓塞进行大脑中动脉闭塞。闭塞后一小时,单独或与NBO(60%),EtOH(1.0 g / kg)或TH(33°C)一起单独或与组织型纤溶酶原激活剂(t-PA)一起给药。在t-PA诱导的再灌注后24小时评估神经功能缺损评分和梗塞体积。在t-PA后3和24小时测量PDH活性和活性氧(ROS)水平。Western印迹用于检测PDH和丙酮酸脱氢酶激酶(PDK)蛋白表达。在缺血大鼠中进行t-PA后,NBO联合TH或EtOH最有效地减少了梗塞体积和神经功能缺损。组合疗法使PDH活性和蛋白质表达增加更多,以及PDK表达减少更多。与单一疗法相比,联合疗法在ROS产生方面的降幅最大。用t-PA再加上60%NBO再灌注可改善氧化损伤并改善PDH调节,从而改善EtOH或TH在神经保护中的功效。当用EtOH或TH进行治疗时,发现具有类似的神经保护作用,提示了类似的神经保护机制以及在临床环境中用EtOH替代TH的可能性。©2016 Wiley Periodicals,Inc.