Department of Anesthesiology, The Fourth Affiliated Hospital, Harbin Medical University, No. 37, Yiyuan Street, Nangang District, 150001 Harbin, China.
Department of Anesthesiology, The Fourth Affiliated Hospital, Harbin Medical University, No. 37, Yiyuan Street, Nangang District, 150001 Harbin, China.
Neuropharmacology. 2014 Feb;77:358-68. doi: 10.1016/j.neuropharm.2013.08.029. Epub 2013 Sep 10.
Propofol has been shown to attenuate brain injury in experimental ischemia models, but few studies have focused on the direct effect of propofol on mitochondrial dysfunction. In this study, we observed the effects of propofol on multiple aspects of mitochondrial dysfunction by studying the mitochondria isolated from rat brains subjected to focal cerebral ischemia-reperfusion. The mitochondria of the cortical tissue were isolated by the Percoll density gradient centrifugation. The isolated mitochondria were fixed and examined with electron microscopy. The calcium-induced mitochondrial swelling was quantified by measuring the decrease in light transmission at 540 nm with a spectrometer. Fluorescent probes were used to selectively stain mitochondria. Flow cytometry was used to measure the membrane potential and the production of reactive oxidative species. Propofol improved the signs of injury in the cortical mitochondria that were exposed to reperfusion following 2 h of focal ischemia. Propofol prevented calcium-induced mitochondrial swelling in a concentration-dependent manner. It did not affect the reperfusion-induced reduction in mitochondrial membrane potential. However, it decreased the production of the mitochondrial reactive oxidative species, which are generated during reperfusion. These results demonstrate that propofol may protect against mitochondrial dysfunction by preventing the ultrastructural change to the mitochondria and the calcium-induced mitochondrial swelling. This protective effect may be mediated by inhibiting the mitochondrial membrane permeability transition and reducing the production of reactive oxidative species in mitochondria.
丙泊酚已被证明可减轻实验性缺血模型中的脑损伤，但很少有研究关注丙泊酚对线粒体功能障碍的直接影响。在这项研究中，我们通过研究大鼠局灶性脑缺血再灌注后分离的线粒体，观察了丙泊酚对线粒体功能障碍多个方面的影响。采用 Percoll 密度梯度离心法分离皮质组织的线粒体。用电子显微镜固定和检查分离的线粒体。通过分光光度计测量 540nm 光透射率的降低来量化钙诱导的线粒体肿胀。使用荧光探针选择性染色线粒体。采用流式细胞术测量膜电位和活性氧物质的产生。丙泊酚可改善皮质线粒体在 2 小时局灶性缺血后再灌注时的损伤迹象。丙泊酚以浓度依赖性方式防止钙诱导的线粒体肿胀。它不影响再灌注引起的线粒体膜电位降低。然而，它减少了再灌注期间产生的线粒体活性氧物质的产生。这些结果表明，丙泊酚可能通过防止线粒体超微结构改变和钙诱导的线粒体肿胀来保护线粒体功能障碍。这种保护作用可能是通过抑制线粒体膜通透性转换和减少线粒体中活性氧物质的产生来介导的。
