State Key Laboratory of Natural and Biomimetic Drugs, Department of Chemical Biology, School of Pharmaceutical Sciences, Peking University, Beijing, China.
CNS Neurosci Ther. 2012 Oct;18(10):811-8. doi: 10.1111/j.1755-5949.2012.00380.x. Epub 2012 Aug 31.
Manganese superoxide dismutase (MnSOD), one of the most crucial antioxidant enzymes in the central nervous system, is thought to be one of the major mechanisms by which cells counteract the injuries of reactive oxygen species after cerebral ischemia. In this study, we used a novel synthesized compound (MnTm4PyP) with highly effective superoxide dismutase activity to study the therapeutic potential of MnSOD and the possible underlying mechanisms in cerebral ischemia.
Primary cultured cortical neurons were used to examine the protective effect of the compounds. Mice with middle cerebral artery occlusion were used as ischemic stroke animal model. Animals were pretreated with MnTm4PyP intravenously 30 min before surgery. At 24 h after surgery, neurological behavior and histological function were observed. Infarcted cortex tissues and cultured neurons were collected for investigation of the oxidative stress signaling pathways.
In vitro studies revealed that MnSOD mimic MnTm4PyP pretreatment significantly increased viability of neurons after injury by H(2) O(2) . Intracellular superoxide radical levels were eliminated. In vivo experiments demonstrated MnTm4PyP pretreatment reduced infarct volume and improved neurological function. The MnSOD mimic alleviated oxidative stress and apoptosis.
MnSOD is an effective therapeutic target in ischemic stroke prevention because of its antioxidant effects and oxidative stress regulation.
锰超氧化物歧化酶（MnSOD）是中枢神经系统中最重要的抗氧化酶之一，被认为是细胞对抗脑缺血后活性氧损伤的主要机制之一。在这项研究中，我们使用了一种新型合成化合物（MnTm4PyP），具有高效的超氧化物歧化酶活性，研究了 MnSOD 的治疗潜力及其在脑缺血中的可能潜在机制。
原代培养皮质神经元用于检测化合物的保护作用。采用大脑中动脉闭塞法制备小鼠脑缺血模型。动物在手术前 30 分钟静脉注射 MnTm4PyP 进行预处理。术后 24 小时观察神经行为和组织学功能。收集梗死皮质组织和培养的神经元，研究氧化应激信号通路。
体外研究表明，MnSOD 模拟物 MnTm4PyP 预处理可显著增加 H 2 O 2 损伤后神经元的活力。消除了细胞内超氧自由基水平。体内实验表明，MnTm4PyP 预处理可减少梗死体积，改善神经功能。MnSOD 模拟物减轻了氧化应激和细胞凋亡。
MnSOD 具有抗氧化作用和氧化应激调节作用，是预防缺血性中风的有效治疗靶点。
