Stabilization of mitochondrial function by tetramethylpyrazine protects against kainate-induced oxidative lesions in the rat hippocampus
Stabilization of mitochondrial function by tetramethylpyrazine protects against kainate-induced oxidative lesions in the rat hippocampus
复制标题
四甲基吡嗪稳定线粒体功能可防止大鼠海马红藻氨酸诱导的氧化损伤
DOI：
10.1016/j.freeradbiomed.2009.12.004
复制
发表时间：
2010-02-15
影响因子：
7.4
通讯作者：
Jia, Hong-Ti
中科院分区：
文献类型：
--
作者：
Li, Shu-Yan;Jia, Yu-Hong;Jia, Hong-Ti
线粒体是细胞死亡的关键调节器。在钙离子介导的谷氨酸受体激活导致神经元变性的作用中，活性氧自由基(ROS)是治疗心脑血管缺血性疾病的主要成分川芎嗪(TMP)，但其对谷氨酸受体过度激活所致的氧化性脑损伤的保护作用在本研究中尚不清楚。我们在体外和体内证明了TMP对红藻氨酸诱导的兴奋性毒性的神经保护作用。我们发现TMP可以部分缓解红藻氨酸诱导的大鼠癫痫持续状态，并预防和挽救海马CA3区的神经元丢失，但不能预防和挽救CA1区的神经元丢失。TMP对神经元丢失的部分预防和拯救归因于保护线粒体结构和功能的完整性，这是通过维持线粒体膜电位来证明的。ATP的产生，以及复杂的I和III活动。线粒体功能的稳定与观察到TMP可以作为还原剂/抗氧化剂来淬灭ROS，阻断脂质过氧化，并保护谷胱甘肽过氧化物酶和谷胱甘肽还原酶等酶类抗氧化剂有关。这些结果提示TMP可能通过猝灭ROS来稳定线粒体功能，从而对氧化性脑损伤产生保护作用。(C)2009 Elsevier Inc.保留所有权利。
Mitochondria are critical regulators of cell death. a key feature of neurodegeneration Reactive oxygen species (ROS) are crucial to Ca2+-mediated effects of glutamate receptor activation leading to neuronal degeneration Tetramethylpyrazine (TMP) is a principal ingredient of Ligusticum wallicht Franchat (a Chinese herb), used for treatment of cardiovascular and cerebrovascular ischemic diseases However, its protection against oxidative brain injury associated with excessive activation of glutamate receptors is unknown In this study, we demonstrate TMP neuroprotection against kainate-induced excitotoxicity in vitro and in vivo We found that TMP could partly alleviate kainate-induced status epilepticus in rats and prevented and rescued neuronal loss in the hippocampal CA3 but not the CA1 region The partial prevention and rescue of neuronal loss by TMP were attributable to the preservation of the structural and functional integrity of mitochondrial evidenced by maintaining the mitochondrial membrane potential. ATP production, and complex I and III activities. Stabilization of mitochondrial function was linked to the observation that TMP could function as a reductant/antioxidant to quench ROS, block lipid peroxidation, and protect enzymatic antioxidants such as glutathione peroxidase and glutathione reductase. These results suggest that TMP may protect against oxidative brain injury by stabilization of mitochondrial function through quenching of ROS. (C) 2009 Elsevier Inc. All rights reserved.