Acupuncture and Tuina School, Chengdu University of Traditional Chinese Medicine, Sichuan Provincial Key Laboratory for Acupuncture & Chronobiology, Key Laboratory of Acupuncture for Senile Disease (Chengdu University of TCM), Ministry of Education, Chengdu 610075, P. R. China.
School of Basic Medical Sciences, Chengdu University of Traditional Chinese Medicine Chengdu 611137, P. R. China.
Am J Chin Med. 2023;51(5):1127-1151. doi: 10.1142/S0192415X23500520. Epub 2023 Jun 17.
The brain metabolic changes caused by the interruption of blood supply are the initial factors of brain injury in ischemic stroke. Electroacupuncture (EA) pretreatment has been shown to protect against ischemic stroke, but whether its neuroprotective mechanism involves metabolic regulation remains unclear. Based on our finding that EA pretreatment significantly alleviated ischemic brain injury in mice by reducing neuronal injury and death, we performed a gas chromatography-time of flight mass spectrometry (GC-TOF/MS) to investigate the metabolic changes in the ischemic brain and whether EA pretreatment influenced these changes. First, we found that some glycolytic metabolites in the normal brain tissues were reduced by EA pretreatment, which may lay the foundation of neuroprotection for EA pretreatment against ischemic stroke. Then, 6[Formula: see text]h of cerebral ischemia-induced brain metabolic changes, especially the enhanced glycolysis, were partially reversed by EA pretreatment, which was manifested by the brain levels of 11 of 35 up-regulated metabolites and 18 of 27 down-regulated metabolites caused by cerebral ischemia significantly decreasing and increasing, respectively, due to EA pretreatment. A further pathway analysis showed that these 11 and 18 markedly changed metabolites were mainly involved in starch and sucrose metabolism, purine metabolism, aspartate metabolism, and the citric acid cycle. Additionally, we found that EA pretreatment raised the levels of neuroprotective metabolites in both normal and ischemic brain tissues. In conclusion, our study revealed that EA pretreatment may attenuate the ischemic brain injury by inhibiting glycolysis and increasing the levels of some neuroprotective metabolites.
脑代谢变化引起的血液供应中断是缺血性中风脑损伤的初始因素。电针(EA)预处理已被证明可以预防缺血性中风,但它的神经保护机制是否涉及代谢调节尚不清楚。基于我们发现 EA 预处理通过减少神经元损伤和死亡显著减轻了小鼠的缺血性脑损伤,我们进行了气相色谱-飞行时间质谱(GC-TOF/MS)分析,以研究缺血性脑内的代谢变化,以及 EA 预处理是否影响这些变化。首先,我们发现 EA 预处理降低了正常脑组织中的一些糖酵解代谢物,这可能为 EA 预处理对缺血性中风的神经保护作用奠定基础。然后,6[Formula: see text]h 脑缺血引起的脑代谢变化,特别是增强的糖酵解,部分被 EA 预处理逆转,这表现为由于 EA 预处理,脑缺血引起的 35 个上调代谢物中的 11 个和 27 个下调代谢物中的 18 个分别显著降低和增加。进一步的途径分析表明,这些 11 个和 18 个明显变化的代谢物主要涉及淀粉和蔗糖代谢、嘌呤代谢、天冬氨酸代谢和柠檬酸循环。此外,我们发现 EA 预处理提高了正常和缺血脑组织中神经保护代谢物的水平。总之,我们的研究表明,EA 预处理可能通过抑制糖酵解和增加一些神经保护代谢物的水平来减轻缺血性脑损伤。