Neuroprotective effect of propofol on necrosis and apoptosis following oxygen-glucose deprivation - Relationship between mitochondrial membrane potential and mode of death
Neuroprotective effect of propofol on necrosis and apoptosis following oxygen-glucose deprivation - Relationship between mitochondrial membrane potential and mode of death
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DOI：
10.1016/j.brainres.2006.04.117
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发表时间：
2006-07-12
期刊：
影响因子：
2.9
通讯作者：
Huaa, Yasuhide
中科院分区：
文献类型：
--
作者：
Iijima, Takehiko;Mishima, Tatsuya;Huaa, Yasuhide
线粒体膜电位（mitochondrialmembranepotential，MMP）在细胞凋亡级联反应中起重要作用，已被提出作为细胞凋亡或坏死的一个指标。我们研究了异丙酚对死亡模式的神经保护作用，重点是MMP。海马神经细胞培养分为对照组、缺氧缺糖30 min组（30 OGD）、缺氧缺糖90 min组（90 OGD）。将丙泊酚以0 μ M（溶媒）、0.1 μ M（Pro0.1）或1.0 μ M（Pro1.0）的浓度加入到每个培养组中。MMP表示为标准化的JC-1荧光。使用荧光素酶-荧光素酶反应测定ATP含量。还评估了神经元活力和细胞凋亡的出现。OGD后ATP含量降低（0.276 +/- 0.115 μ M/μ g（对照），0.172 +/- 0.125 μ M/μ g（30 OGD）和0.096 +/- 0.092 μ M/μ g（90 OGD））。异丙酚不改变ATP含量。30 OGD后MMP呈超极化（1.26 +/- 0.23（溶剂），1.29 +/- 0.13（Pro0.1）和1.18 +/- 0.06（Pro1.0）），但在90 OGD后去极化（0.77 ± 0.04（载体），0.89 ± 0.04（Pro0.1），但Pro1.0阻止去极化（1.03 ± 0.15（P < 0.05））。90 OGD后，细胞活力显著降低至50.3 +/- 5.7%（溶剂）、46.1 +/- 7.5%（Pro0.1），但Pro1.0显著挽救了65.1 +/- 6.2%的神经元（高于溶剂和Pro0.1值，P < 0.05）。在OGD后24 h，30 OGD组中TUNEL阳性细胞增加至34.5 +/- 6.2%（溶剂）、26.7 +/- 7.9%（Pro0.1）和30.4 +/- 7.1%（Pro1.0）。异丙酚对细胞凋亡的发生率没有药理学作用，异丙酚抑制急性神经元死亡，同时维持MMP，但不能阻止随后的细胞凋亡。异丙酚诱导神经元死亡暂停，在此期间，药物干预可能能够防止细胞死亡。(c)2006 Elsevier B. V.保留所有权利。
Mitochondrial membrane potential (MMP) appears to play an important role in apoptotic cascade and has been proposed as an index for apoptosis or necrosis. We examined the neuroprotective effect of propofol on mode of death, focusing on MMP. Hippocampal cell culture was divided into three groups: control, oxygen-glucose deprivation for 30 min (30OGD), 90 min (90OGD). Propofol was added to each culture group at a concentration of 0 mu M (Vehicle), 0.1 mu M (Pro0.1) or 1.0 mu M (Pro1.0). MMP was expressed as normalized JC-1 fluorescence. ATP content was assayed using the luciferin-luciferase reaction. Neuronal viability and appearance of apoptosis were also assessed. ATP content was decreased after OGD (0.276 +/- 0.115 mu M/mu g (control), 0.172 +/- 0.125 mu M/mu g (30OGD) and 0.096 +/- 0.092 mu M/mu g (90OGD)). Propofol did not alter ATP content. MMP was hyperpolarized after 30OGD (1.26 +/- 0.23 (vehicle), 1.29 +/- 0.13 (Pro0.1) and 1.18 +/- 0.06 (Pro1.0)) but was depolarized after 90OGD (0.77 +/- 0.04 (vehicle), 0.89 +/- 0.04 (Pro0.1), but Pro1.0 prevented depolarization (1.03 +/- 0.15 (P < 0.05)). Viability of cells significantly decreased to 50.3 +/- 5.7% (vehicle), 46.1 +/- 7.5% (Pro0.1), but Pro1.0 significantly salvaged neurons 65.1 +/- 6.2% (higher than vehicle and Pro0.1 value, P < 0.05) after 90OGD. At 24 h after OGD, TUNEL-positive cells were increased to 34.5 +/- 6.2% (vehicle), 26.7 +/- 7.9% (Pro0.1) and 30.4 +/- 7.1% (Pro1.0) in the 30OGD group. No pharmacological effect of propofol on the incidence of apoptosis was found. Propofol inhibited acute neuronal death accompanied with the maintenance of MMP but did not prevent subsequent apoptosis. Propofol induces a moratorium on neuronal death, during which pharmacological intervention might be able to prevent cell death. (c) 2006 Elsevier B.V. All rights reserved.