Department of Anesthesiology, The Fourth Affiliated Hospital of the Harbin Medical University, 37 Yiyuan Road, Harbin, 150001, Heilongjiang, China.
Neurochem Res. 2018 Feb;43(2):420-429. doi: 10.1007/s11064-017-2437-z. Epub 2017 Nov 22.
Oxidative stress caused by mitochondrial dysfunction during reperfusion is a key pathogenic mechanism in cerebral ischemia-reperfusion (IR) injury. Propofol (2,6-diisopropylphenol) has been proven to attenuate mitochondrial dysfunction and reperfusion injury. The current study reveals that propofol decreases oxidative stress injury by preventing succinate accumulation in focal cerebral IR injury. We evaluated whether propofol could attenuate ischemic accumulation of succinate in transient middle cerebral artery occlusion in vivo. By isolating mitochondria from cortical tissue, we also examined the in vitro effects of propofol on succinate dehydrogenase (SDH) activity and various mitochondrial bioenergetic parameters related to oxidative stress injury, such as the production of reactive oxidative species, membrane potential, Ca-induced mitochondrial swelling, and morphology via electron microscopy. Propofol significantly decreased the ischemic accumulation of succinate by inhibiting SDH activity and inhibited the oxidation of succinate in mitochondria. Propofol can decrease membrane potential in normal mitochondria but not in ischemic mitochondria. Propofol prevents Ca-induced mitochondrial swelling and ultrastructural changes to mitochondria. The protective effect of propofol appears to act, at least in part, by limiting oxidative stress injury by preventing the ischemic accumulation of succinate.
再灌注期间线粒体功能障碍引起的氧化应激是脑缺血再灌注 (IR) 损伤的关键发病机制。丙泊酚（2,6-二异丙基苯酚）已被证明可减轻线粒体功能障碍和再灌注损伤。本研究揭示，丙泊酚通过防止琥珀酸在局灶性脑 IR 损伤中积累来减轻氧化应激损伤。我们评估了丙泊酚是否可以减轻体内短暂性大脑中动脉闭塞引起的缺血性琥珀酸积累。通过从皮质组织中分离线粒体，我们还研究了丙泊酚对琥珀酸脱氢酶 (SDH) 活性的体外作用，以及与氧化应激损伤相关的各种线粒体生物能学参数，例如活性氧物质的产生、膜电位、Ca 诱导的线粒体肿胀和形态通过电子显微镜。丙泊酚通过抑制 SDH 活性显著减少缺血性琥珀酸的积累，并抑制线粒体中琥珀酸的氧化。丙泊酚可降低正常线粒体中的膜电位，但不能降低缺血性线粒体中的膜电位。丙泊酚可防止 Ca 诱导的线粒体肿胀和超微结构变化。丙泊酚的保护作用似乎至少部分通过防止缺血性琥珀酸积累来限制氧化应激损伤而起作用。
