HMG CoA reductase inhibitors reduce ischemic brain injury of Wistar rats through decreasing oxidative stress on neurons
HMG CoA reductase inhibitors reduce ischemic brain injury of Wistar rats through decreasing oxidative stress on neurons
复制标题
DOI：
10.1016/j.brainres.2004.12.051
复制
发表时间：
2005-03-10
期刊：
影响因子：
2.9
通讯作者：
Abe, K
中科院分区：
文献类型：
--
作者：
Hayashi, T;Hamakawa, K;Abe, K
他汀类药物具有针对缺血性损伤的神经保护作用，但其如何保护神经元尚不清楚。我们推测与他汀类药物的抗氧化特性有关，并研究了他汀类药物对缺血后大脑氧化神经元损伤的影响。给予阿托伐他汀、匹伐他汀、辛伐他汀或载体14天后，对Wistar大鼠进行大脑中动脉闭塞90分钟。再灌注后第 1 天，研究了氧化应激标记物 4-羟基壬烯醛 (HNE) 和 8-羟基-2-脱氧鸟苷 (8-OHdG) 的产生以及梗死形成。在媒介物组中，确认了大面积梗塞，并大量产生了FINE和8-OHdG。在他汀类药物治疗组中，梗塞更小，并且 HNE 和 8-OHdG 的产生不如媒介物组那么显着。在所研究的他汀类药物中，辛伐他汀对于减少氧化应激和梗塞体积最有效，这可能是由于其高亲脂性所致。他汀类药物减少氧化应激可能是改善大鼠缺血性脑损伤的主要原因之一。 (c) 2005 Elsevier B.V. 保留所有权利。
Statins possess neuroprotective effect against ischemic damage, but how they protect neurons is not exactly made clear. We speculated that anti-oxidative property of statins is implicated, and investigated statins' influences on the oxidative neuronal damage in the brain after ischemia. After 14 days of atorvastatin, pitavastatin, simvastatin, or vehicle administration, 90 min of middle cerebral artery occlusion was imposed on Wistar rats. The production of 4-hydroxynonenal (HNE) and 8-hydroxy-2-deoxyguanosine (8-OHdG), both of which are oxidative stress markers, as well as infarction formation were investigated at 1 day after the reperfusion. In the vehicle group, massive infarction was confirmed and FINE and 8-OHdG are robustly produced. In the statins-treated group, the infarction was smaller and the HNE and 8-OHdG production was less prominent than the vehicle group. Among the statins investigated, simvastatin was most effective for reducing oxidative stress and infarction volume, which may be brought by its highly lipophilic property. Reduction of oxidative stress by statins may be one main reason in ameliorating ischemic brain damage in rats. (c) 2005 Elsevier B.V. All rights reserved.