The Synergistic Neuroprotective Effects of Combined Rosuvastatin and Resveratrol Pretreatment against Cerebral Ischemia/Reperfusion Injury
The Synergistic Neuroprotective Effects of Combined Rosuvastatin and Resveratrol Pretreatment against Cerebral Ischemia/Reperfusion Injury
复制标题
瑞舒伐他汀联合白藜芦醇预处理对脑缺血/再灌注损伤的协同神经保护作用
DOI：
10.1016/j.jstrokecerebrovasdis.2018.01.033
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发表时间：
2018-06-01
影响因子：
2.5
通讯作者：
Wang, CuiLan
中科院分区：
文献类型：
--
作者：
Liu, Ying;Yang, HongNa;Wang, CuiLan
背景资料：瑞舒伐他汀和白藜芦醇通过共同的途径对脑缺血/再灌注损伤发挥神经保护作用。白藜芦醇还被证明通过增强自噬来保护脑缺血/再灌注损伤。因此，我们假设瑞舒伐他汀和白藜芦醇联合预处理对脑缺血/再灌注损伤具有协同作用。材料与方法：采用成年雄性Sprague道利大鼠行大脑中动脉闭塞术，建立脑缺血再灌注损伤模型，随机分为4组：对照组、白藜芦醇组、瑞舒伐他汀组、瑞舒伐他汀+白藜芦醇组。在脑缺血发作前给予瑞舒伐他汀（10 mg/kg）或白藜芦醇（50 mg/kg），每天1次，共7天。结果如下：我们发现，与单独使用白藜芦醇或瑞舒伐他汀单独使用预处理组相比，瑞舒伐他汀和白藜芦醇联合预处理不仅显著降低神经功能缺损评分、脑梗死体积、caspase-3和白细胞介素-1 β（IL-1 β）水平，而且显著增加Bcl-2/Bax和LC 3 II/LC 3 I比值以及Becline-1水平。瑞舒伐他汀单独预处理显著增加了LC 3 II/LC 3 I比值和Beclin-1水平。但在神经功能缺损评分、脑梗死体积、caspase-3、IL-1 β、Beclin-1水平、Bcl-2/Bax和LC 3 II/LC 3 I比值方面，两组间差异无统计学意义。结论：协同增强的抗凋亡、抗炎和自噬激活可能是瑞舒伐他汀与白藜芦醇联合对脑缺血/再灌注损伤的协同神经保护作用的原因。
Background: It is well accepted that both rosuvastatin and resveratrol exert neuroprotective effects on cerebral ischemia/reperfusion injury through some common pathways. Resveratrol has also been demonstrated to protect against cerebral ischemia/reperfusion injury through enhancing autophagy. Thus, we hypothesized that combined rosuvastatin and resveratrol pretreatment had synergistic effects on cerebral ischemia/reperfusion injury. Materials and Methods: Adult male Sprague Dawley rats receiving middle cerebral artery occlusion surgery as animal model of cerebral ischemia/reperfusion injury were randomly assigned to 4 groups: control, resveratrol alone pretreatment, rosuvastatin alone pretreatment, and combined rosuvastatin and resveratrol pretreatment. Rosuvastatin (10 mg/kg) or resveratrol (50 mg/kg) was administrated once a day for 7 days before cerebral ischemia onset. Results: We found that combined rosuvastatin and resveratrol pretreatment not only significantly decreased the neurologic defective score, cerebral infarct volume, the levels of caspase-3, and Interleukin-1 beta (IL-1 beta) but also significantly increased the ratios of Bcl-2/Bax and LC3II/LC3I, as well as the level of Becline-1, compared with resveratrol alone or rosuvastatin alone pretreatment group. Rosuvastatin alone pretreatment significantly increased the ratio of LC3II/LC3I and the level of Beclin-1. However, there were no significant differences in the neurologic defective score, cerebral infarct volume, the levels of caspase-3, IL-1 beta, and Beclin-1, and the ratios of Bcl-2/Bax and LC3II/LC3I between resveratrol pretreatment group and rosuvastatin pretreatment group. Conclusions: Synergistically enhanced antiapoptosis, anti-inflammation, and autophagy activation might be responsible for the synergistic neuroprotective effects of combining rosuvastatin with resveratrol on cerebral ischemia/reperfusion injury.