Ginkgo biloba extract neuroprotective action is dependent on heme oxygenase 1 in ischemic reperfusion brain injury.
Ginkgo biloba extract neuroprotective action is dependent on heme oxygenase 1 in ischemic reperfusion brain injury.
复制标题
银杏提取物神经保护作用取决于缺血性再灌注脑损伤中血红素氧酶1。
DOI：
10.1161/strokeaha.108.523480
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发表时间：
2008-12
期刊：
影响因子：
8.3
通讯作者：
Doré S
中科院分区：
文献类型：
--
作者：
Saleem S;Zhuang H;Biswal S;Christen Y;Doré S
据报道，银杏叶提取物对健康有益，特别是对大脑有药用价值，目前在多个国家被用作处方药。据报道，标准化银杏提取物 EGb761 可以保护神经元免受氧化应激，但其潜在机制尚不完全清楚。为了表征短暂性缺血中 EGb761 的口服消耗，我们在野生型和血红素加氧酶 1 (HO-1) 敲除中进行了大脑中动脉闭塞 (MCAO) 丝模型。小鼠在短暂闭塞前预处理7天，或在再灌注期间进行急性后处理；然后评估神经行为评分和梗塞体积。此外，原代皮质神经元培养物用于研究抗氧化酶 HO-1 在 EGb761 相关细胞保护中的贡献。与载体治疗的小鼠相比，用 EGb761 预处理的小鼠神经功能障碍减少了 50.9±5.6%，梗塞体积减少了 48.2±5.3%；这种效应在 HO-1 敲除中被消除。除了 EGb761 的预防特性外，再灌注后 5 分钟和 4.5 小时的急性后处理也导致梗塞面积显着减小（P<0.01）。我们之前证明 EGb761 在神经元培养物中以剂量和时间依赖性方式显着诱导 HO-1 水平，在此我们揭示了这种从头开始的 HO-1 诱导对于神经保护免受自由基损伤和兴奋性毒性是必需的，因为它被酶抑制剂显着减弱。这些结果证明 EGb761 可用作脑缺血的预防或治疗剂，并表明 HO-1 至少部分有助于 EGb761 神经保护。
Ginkgo biloba extracts are now prescribed in several countries for their reported health benefits, particularly for medicinal properties in the brain. The standardized Ginkgo extract, EGb761, has been reported to protect neurons against oxidative stress, but the underlying mechanisms are not fully understood. To characterize the oral consumption of EGb761 in transient ischemia, we performed the middle cerebral artery occlusion (MCAO) filament model in wild-type and heme oxygenase 1 (HO-1) knockouts. Mice were pretreated for 7 days before the transient occlusion or posttreated acutely during reperfusion; then neurobehavioral scores and infarct volumes were assessed. Furthermore, primary cortical neuronal cultures were used to investigate the contribution of the antioxidant enzyme HO-1 in the EGb761-associated cytoprotection. Mice that were pretreated with EGb761 had 50.9±5.6% less neurological dysfunction and 48.2±5.3% smaller infarct volumes than vehicle-treated mice; this effect was abolished in HO-1 knockouts. In addition to the prophylactic properties of EGb761, acute posttreatment 5 minutes and 4.5 hours after reperfusion also led to significant reduction in infarct size (P<0.01). After our previous demonstration that EGb761 significantly induced HO-1 levels in a dose- and time-dependent manner in neuronal cultures, here we revealed that this de novo HO-1 induction was required for neuroprotection against free radical damage and excitotoxicity as it was significantly attenuated by the enzyme inhibitor. These results demonstrate that EGb761 could be used as a preventive or therapeutic agent in cerebral ischemia and suggest that HO-1 contributes, at least in part, to EGb761 neuroprotection.