电针预处理通过调节内源性大麻素系统诱导对局灶性脑缺血的快速耐受。
Pretreatment with electroacupuncture induces rapid tolerance to focal cerebral ischemia through regulation of endocannabinoid system.
作者信息
Wang Qiang, Peng Ye, Chen Shaoyang, Gou Xingchun, Hu Bo, Du Juan, Lu Yan, Xiong Lize
机构信息
Department of Anesthesiology, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, Shaanxi Province, China.
出版信息
Stroke. 2009 Jun;40(6):2157-64. doi: 10.1161/STROKEAHA.108.541490. Epub 2009 Apr 16.
BACKGROUND AND PURPOSE
Our previous study demonstrated that pretreatment with electroacupuncture (EA) induces rapid tolerance to focal cerebral ischemia. The present study was aimed to investigate the involvement of the endocannabinoid system in the early neuroprotection conferred by EA pretreatment in the animal model of focal cerebral ischemia.
METHODS
Two hours after the end of EA pretreatment, focal cerebral ischemia was induced by middle cerebral artery occlusion for 120 minutes in male Sprague-Dawley rats or male C57BL/6 mice. The neurobehavioral scores, infarction volumes, and neuronal apoptosis were evaluated at 24 hours or 7 days after reperfusion in the presence or absence of AM251 (a selective cannabinoid receptor type 1 [CB1] receptor antagonist) or CB1 short interfering RNA. The expression of CB1 receptor and the content of endocannabinoids in the brains were also investigated.
RESULTS
EA pretreatment reduced infarct size, improved neurological outcome, and inhibited neuronal apoptosis at 24 hours or 7 days after reperfusion. The beneficial effects were abolished by AM251. CB1 knockdown by CB1 short interfering RNA attenuated EA pretreatment-induced neuroprotection. EA pretreatment upregulated the neuronal expression of CB1 receptor in the rat brains and elevated the brain tissue content of the endocannabinoid 2-arachidonylglycerol and N-arach-idonoylethanolamine-anandamide. Pretreatment with 2-arachidonylglycerol and N-arach-idonoylethanolamine-anandamide also reduced infarct size and improved neurological outcome.
CONCLUSIONS
We conclude that pretreatment with EA increases the production of endocannabinoid 2-arachidonylglycerol and N-arach-idonoylethanolamine-anandamide, which elicits protective effects against transient cerebral ischemia through CB1 receptors. These results suggest a novel mechanism of EA pretreatment-induced rapid tolerance to focal cerebral ischemia.
背景与目的
我们之前的研究表明，电针预处理可诱导对局灶性脑缺血的快速耐受。本研究旨在探讨内源性大麻素系统在电针预处理对局灶性脑缺血动物模型早期神经保护作用中的作用机制。
方法
在雄性Sprague-Dawley大鼠或雄性C57BL/6小鼠中，电针预处理结束2小时后，通过大脑中动脉闭塞120分钟诱导局灶性脑缺血。在再灌注后24小时或7天时，在有或没有AM251（一种选择性1型大麻素受体[CB1]拮抗剂）或CB1小干扰RNA的情况下，评估神经行为评分、梗死体积和神经元凋亡情况。同时还研究了大脑中CB1受体的表达和内源性大麻素的含量。
结果
电针预处理可减少再灌注后24小时或7天时的梗死面积，改善神经功能结局，并抑制神经元凋亡。AM251可消除这些有益作用。CB1小干扰RNA敲低CB1可减弱电针预处理诱导的神经保护作用。电针预处理上调了大鼠大脑中CB1受体的神经元表达，并提高了内源性大麻素2-花生四烯酸甘油酯和N-花生四烯酰乙醇胺（即花生四烯酸乙醇胺）的脑组织含量。用2-花生四烯酸甘油酯和N-花生四烯酰乙醇胺预处理也可减少梗死面积并改善神经功能结局。
结论
我们得出结论，电针预处理可增加内源性大麻素2-花生四烯酸甘油酯和N-花生四烯酰乙醇胺的产生，它们通过CB1受体对短暂性脑缺血发挥保护作用。这些结果提示了电针预处理诱导对局灶性脑缺血快速耐受的新机制。
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