Electroacupuncture (EA) pretreatment induces cerebral ischemic tolerance; however, the mechanism remains poorly understood. This study aimed to determine the participation of peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α)-mediated mitochondrial biogenesis in the neuroprotection of EA and whether cannabinoid receptor 1 (CB1R) is involved in this mechanism. At 2 hours after EA pretreatment, adult male C57BL/6j mice were subjected to 60-minute right middle cerebral artery occlusion (MCAO). Mitochondrial function, the level of mitochondrial biogenesis-related proteins (nuclear transcription factor 1, NRF1; mitochondrial transcription factor A, TFAM), and mitochondrial DNA (mtDNA) were measured. A small interfering RNA (siRNA) targeting PGC-1α and the CB1R antagonists AM251 and SR141716A were given to the animals before EA pretreatment, and mitochondrial function and biogenesis were examined after MCAO. EA ameliorated the mitochondrial function, upregulated the NRF1 and TFAM expression, and increased the mtDNA levels and the volume and number of mitochondria. EA pretreatment increased the expression of PGC-1α, whereas the PGC-1α siRNA and CB1R antagonists reversed the improved neuroprotection and increased mitochondrial biogenesis induced by EA. Our results indicated that EA pretreatment protects the mitochondria and promotes mitochondrial biogenesis by activating CB1R-dependent PGC-1α, which provides a novel mechanism for EA pretreatment-induced ischemic tolerance.

中文翻译：

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CB1R 依赖性 PGC-1α 的激活参与电针预处理诱导的线粒体生物发生的改善

电针（EA）预处理诱导脑缺血耐受；然而，人们对该机制仍知之甚少。本研究旨在确定过氧化物酶体增殖物激活受体 γ 共激活因子-1α ( PGC-1α ) 介导的线粒体生物发生在 EA 的神经保护中的参与，以及大麻素受体 1 (CB1R) 是否参与该机制。在 EA 预处理后 2 小时，成年雄性 C57BL/6j 小鼠接受 60 分钟的右大脑中动脉闭塞 (MCAO)。测量线粒体功能、线粒体生物发生相关蛋白（核转录因子 1，NRF1；线粒体转录因子 A，TFAM）和线粒体 DNA (mtDNA) 的水平。靶向PGC-1α 的小干扰 RNA (siRNA)在EA预处理前给予动物CB1R拮抗剂AM251和SR141716A，在MCAO后检查线粒体功能和生物发生。EA 改善线粒体功能，上调 NRF1 和 TFAM 表达，增加 mtDNA 水平以及线粒体的体积和数量。EA 预处理增加了PGC-1α 的表达，而PGC-1α siRNA 和 CB1R 拮抗剂逆转了 EA 诱导的改善的神经保护和增加的线粒体生物发生。我们的结果表明，电针预处理通过激活 CB1R 依赖性PGC-1α来保护线粒体并促进线粒体生物发生，这为电针预处理诱导的缺血耐受提供了一种新机制。