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首页> 外文期刊>Biochemical Pharmacology >Neuroprotective effects of PMC, a potent alpha-tocopherol derivative, in brain ischemia-reperfusion: reduced neutrophil activation and anti-oxidant actions.
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Neuroprotective effects of PMC, a potent alpha-tocopherol derivative, in brain ischemia-reperfusion: reduced neutrophil activation and anti-oxidant actions.

机译：PMC（一种有效的α-生育酚衍生物）在脑缺血再灌注中的神经保护作用：减少中性粒细胞的活化和抗氧化作用。

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摘要

2,2,5,7,8-Pentamethyl-6-hydroxychromane (PMC) is the most potent analogue of alpha-tocopherol for anti-oxidation. It is more hydrophilic than other alpha-tocopherol derivatives and has potent free radical-scavenging activity. In the present study, PMC significantly attenuated middle cerebral artery occlusion (MCAO)-induced focal cerebral ischemia in rats. Administration of PMC at 20mg/kg, showed marked reductions in infarct size compared with that of control rats. MCAO-induced focal cerebral ischemia was associated with increases in HIF-1alpha, active caspase-3, iNOS, and nitrotyrosine expressions in ischemic regions. These expressions were markedly inhibited by treatment with PMC (20mg/kg). In addition, PMC (4-12 microM) inhibited respiratory bursts in human neutrophils stimulated by fMLP (800 nM) and PMA (320 nM). Furthermore, PMC (6, 12, and 60 microM) also significantly inhibited neutrophil migration stimulated by leukotriene B(4) (160 nM). An electron spin resonance (ESR) method was conducted on the scavenging activity of PMC on the free radicals formed. PMC (12 microM) greatly reduced the ESR signal intensities of superoxide anion, hydroxyl radical, and methyl radical formation. In conclusion, we demonstrate a potent neuroprotective effect of PMC on MCAO-induced focal cerebral ischemia in vivo. This effect may be mediated, at least in part, by inhibition of free radical formation, followed by inhibition of HIF-1alpha activation, apoptosis formation (active caspase-3), neutrophil activation, and inflammatory responses (i.e., iNOS and nitrotyrosine expressions), resulting in a reduction in the infarct volume in ischemia-reperfusion brain injury. Thus, PMC treatment may represent a novel approach to lowering the risk or improving function in ischemia-reperfusion brain injury-related disorders.
机译：2,2,5,7,8-五甲基-6-羟基苯并二氢吡喃（PMC）是最有效的抗氧化剂α-生育酚类似物。它比其他α-生育酚衍生物更具亲水性，并具有有效的清除自由基活性。在本研究中，PMC显着减轻了大鼠大脑中动脉闭塞（MCAO）引起的局灶性脑缺血。与对照组相比，以20mg / kg的PMC给药显示梗塞面积明显减少。 MCAO诱导的局灶性脑缺血与缺血区域HIF-1alpha，活性caspase-3，iNOS和硝基酪氨酸表达的增加有关。用PMC（20mg / kg）处理可明显抑制这些表达。此外，PMC（4-12 microM）抑制了由fMLP（800 nM）和PMA（320 nM）刺激的人中性粒细胞的呼吸爆发。此外，PMC（6、12和60 microM）也显着抑制白三烯B（4）（160 nM）刺激的嗜中性白细胞迁移。对PMC对形成的自由基的清除活性进行了电子自旋共振（ESR）方法。 PMC（12 microM）大大降低了超氧阴离子，羟基自由基和甲基自由基形成的ESR信号强度。总之，我们证明了PMC在体内对MCAO诱导的局灶性脑缺血具有有效的神经保护作用。此作用可能至少部分地通过抑制自由基形成，其次是抑制HIF-1alpha激活，凋亡形成（活性caspase-3），中性粒细胞激活和炎症反应（即iNOS和硝基酪氨酸表达）来介导。导致缺血再灌注脑损伤的梗塞体积减少。因此，PMC治疗可能代表一种降低缺血再灌注脑损伤相关疾病风险或改善功能的新颖方法。

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