Goreisan Prevents Brain Edema after Cerebral Ischemic Stroke by Inhibiting Aquaporin 4 Upregulation in Mice
Goreisan Prevents Brain Edema after Cerebral Ischemic Stroke by Inhibiting Aquaporin 4 Upregulation in Mice
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DOI：
10.1016/j.jstrokecerebrovasdis.2017.10.010
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发表时间：
2018-03-01
影响因子：
2.5
通讯作者：
Mishima, Kenichi
中科院分区：
文献类型：
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作者：
Nakano, Takafumi;Nishigami, Chisa;Mishima, Kenichi
背景：水通道蛋白4（AQP 4）是一种水选择性转运蛋白，在中枢神经系统星形胶质细胞中表达。脑缺血后AQP 4水平升高，导致缺血性脑水肿。脑水肿通过升高颅内压导致继发性脑损伤，显著影响死亡率和运动功能。因此，AQP 4是改善脑缺血后脑水肿的重要靶点。日本草药汉方药，goreisan，已知抑制AQP 4活性。在这里，我们研究了goreisan是否可以通过AQP 4阻止大脑中动脉闭塞4小时（4小时MCAO）小鼠脑缺血引起的脑水肿。方法：在MCAO前给予Goreisan 500 mg/kg，2次/d，连续5 d。分别采用Western blotting和旋转棒试验检测AQP 4表达和运动协调性。结果：MCAO后4 h小鼠脑含水量在24 h即明显增加。在MCAO后24小时，Goreisan治疗显著降低缺血脑中的脑含水量和AQP 4表达。此外，Goreisan治疗减轻了MCAO后24小时的运动协调缺陷。结论：本研究的结果表明，goreisan可能是一个有用的新的治疗缺血性脑水肿的选择。关键词：Goreisan-脑水肿-水通道蛋白4-脑缺血
Background: Aquaporin 4 (AQP4) is a water-selective transport protein expressed in astrocytes throughout the central nervous system. AQP4 level increases after cerebral ischemia and results in ischemic brain edema. Brain edema markedly influences mortality and motor function by elevating intracranial pressure that leads to secondary brain damage. Therefore, AQP4 is an important target to improve brain edema after cerebral ischemia. The Japanese herbal Kampo medicine, goreisan, is known to inhibit AQP4 activity. Here, we investigated whether goreisan prevents induction of brain edema by cerebral ischemia via AQP4 using 4-hour middle cerebral artery occlusion (4h MCAO) mice. Methods: Goreisan was orally administered at a dose of 500 mg/kg twice a day for 5 days before MCAO. AQP4 expression and motor coordination were measured by Western blotting and rotarod test, respectively. Results: Brain water content of 4h MCAO mice was significantly increased at 24 hours after MCAO. Treatment with goreisan significantly decreased both brain water content and AQP4 expression in the ischemic brain at 24 hours after MCAO. In addition, treatment with goreisan alleviated motor coordination deficits at 24 hours after MCAO. Conclusions: The results of this study suggested that goreisan may be a useful new therapeutic option for ischemic brain edema. Key Words: Goreisan-brain edema-aquaporin 4-cerebral ischemia.