Liu Zhaoyu, Chen Xiyao, Gao Yang, Sun Sisi, Yang Lei, Yang Qianzi, Bai Fuhai, Xiong Lize, Wang Qiang
Department of Anesthesiology, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China.
Department of Physiology, Fourth Military Medical University, Xi'an 710032, China.
Sci Rep. 2015 Apr 1;5:9490. doi: 10.1038/srep09490.
We investigated whether glutamate receptor subunit 2 (GluR2) is involved in EA pretreatment-induced neuroprotection via cannabinoid CB1 receptors (CB1R) after global cerebral ischemia in mice. Two hours after electric acupuncture (EA) pretreatment, global cerebral ischemia (GCI) was induced by bilateral common carotid artery occlusion (BCCAO) for 20 min. The GluR2 expression was examined in the hippocampus after reperfusion. Cell survival, neuronal apoptosis, the Bax/Bcl-2 ratio and neurological scores were evaluated at 24 h after BCCAO in the presence or absence of the GluR2 inhibitor. Furthermore, the GluR2 was determined in the presence and absence of CB1R inhibitor. Our results showed EA pretreatment enhanced expression of GluR2 in the hippocampus 2 h after reperfusion. Moreover, EA pretreatment improved neurological outcome, promoted cell survival, inhibited neuronal apoptosis, and decreased the Bax/Bcl-2 ratio after reperfusion. GluR2 knockdown by GluR2 siRNA effectively reversed the beneficial effects of EA pretreatment. Furthermore, CB1R siRNA and two CB1R antagonists blocked the elevation of GluR2 expression by EA pretreatment, whereas the two CB1R agonists up-regulated GluR2 expression as EA pretreatment. In conclusion, GluR2 up-regulation is involved in neuroprotection of EA pretreatment against GCI through CB1R, suggesting that GluR2 may be a novel target for stroke intervention.
我们研究了在小鼠全脑缺血后，谷氨酸受体亚基2（GluR2）是否通过大麻素CB1受体（CB1R）参与电针（EA）预处理诱导的神经保护作用。电针预处理2小时后，通过双侧颈总动脉闭塞（BCCAO）20分钟诱导全脑缺血（GCI）。再灌注后检测海马中GluR2的表达。在存在或不存在GluR2抑制剂的情况下，于BCCAO后24小时评估细胞存活、神经元凋亡、Bax/Bcl-2比值和神经功能评分。此外，在存在和不存在CB1R抑制剂的情况下测定GluR2。我们的结果显示，电针预处理可增强再灌注后2小时海马中GluR2的表达。此外，电针预处理改善了神经功能结局，促进了细胞存活，抑制了神经元凋亡，并降低了再灌注后的Bax/Bcl-2比值。GluR2 siRNA敲低GluR2有效地逆转了电针预处理的有益作用。此外，CB1R siRNA和两种CB1R拮抗剂阻断了电针预处理引起的GluR2表达升高，而两种CB1R激动剂上调GluR2表达的作用与电针预处理相同。总之，GluR2上调通过CB1R参与电针预处理对GCI的神经保护作用，提示GluR2可能是中风干预的新靶点。
