Department of Anesthesiology, Affiliated Hospital of Qingdao University Medical College, Qingdao 266003, Shandong Province, China.
Neurosci Lett. 2013 Feb 22;535:104-9. doi: 10.1016/j.neulet.2012.12.049. Epub 2013 Jan 9.
Mitochondrial division inhibitor (mdivi-1) is a derivative of quinazolinone that acts as a selective inhibitor of a mitochondrial fission protein Drp1. A previous study demonstrated that as a selective inhibitor of Drp1, mdivi-1 has a protective effect in an experimental model of heart ischemia/reperfusion injury. In this study, we investigated the protective effects of mdivi-1 on cerebral ischemia/reperfusion injury in a middle cerebral artery occlusion mouse model. We found that mdivi-1 (1.2mg/kg) significantly reduced cerebral damage induced by ischemia/reperfusion. This neuroprotective effect was dose-dependent. Mdivi-1 treatment blocked apoptotic cell death in cerebral ischemia/reperfusion injury, and significantly decreased the expression of Drp1 and Cytochrome C. These results suggest that mdivi-1 exerts neuroprotective effects against nerve injury after cerebral ischemia/reperfusion, and the underlying mechanism may be through the prevention of Cytochrome C release and suppression of the mitochondrial apoptosis pathway.
线粒体分裂抑制剂（mdivi-1）是一种喹唑啉酮衍生物，作为一种线粒体分裂蛋白 Drp1 的选择性抑制剂。先前的研究表明，作为 Drp1 的选择性抑制剂，mdivi-1 在心脏缺血/再灌注损伤的实验模型中具有保护作用。在这项研究中，我们在大脑中动脉闭塞的小鼠模型中研究了 mdivi-1 对脑缺血/再灌注损伤的保护作用。我们发现 mdivi-1（1.2mg/kg）可显著减轻缺血/再灌注引起的脑损伤。这种神经保护作用呈剂量依赖性。mdivi-1 治疗可阻止脑缺血/再灌注损伤中的细胞凋亡，显著降低 Drp1 和细胞色素 C 的表达。这些结果表明，mdivi-1 对脑缺血/再灌注后的神经损伤具有神经保护作用，其潜在机制可能是通过防止细胞色素 C 释放和抑制线粒体凋亡途径。
