*The No.2 Clinical Medical College, Nanjing University of Chinese Medicine, Nanjing, Jiangsu 210023, P. R. China.
‡Jiangsu Key Laboratory of Paediatric Respiratory Disease, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, Jiangsu 210029, P. R. China.
Am J Chin Med. 2019;47(5):1025-1041. doi: 10.1142/S0192415X19500526. Epub 2019 Jul 21.
Myocardial infarction (MI), the most common symptom is chest pain, occurs when blood flow decreases or stops to a part of the heart, causing damage to the heart muscle. Electroacupuncture pretreatment (EP) is a recent observation which has been shown to induce ischemic tolerance like the ischemia preconditioning, suggesting that EP may be a promising preventive strategy for individual susceptibility to MI. This study investigated mechanisms that underlie the effect of EP on MI through the use of gas chromatography-mass spectrometry (GC-MS)-based metabolic profiling. Male Sprague-Dawley rats were randomly divided to receive or not receive three days of EP at PC6 (Neiguan). Then on the fourth day, each group was further divided to undergo mock surgery or MI, induced by ligation of the left anterior descending coronary artery. After 24h, the blood samples and hearts were collected for the follow-up research. The results showed that treatment by EP significantly reduced the levels of CK-MB, cTnT, AST, and MDH in serum and decreased myocardial infarction area. According to GC-MS-based serum metabolic profiling and analysis, a total of 636 characteristic peaks were identified, including 158 known and 478 unknown metabolites. MI caused comprehensive metabolic changes in glycolysis-related metabolites, malate-aspartate shuttle (MAS) metabolites, and purine metabolites with anti-oxidant functions, while EP reversed more than half of the differential metabolic changes, mainly affecting amino acid and energy metabolism, especially the glutamate metabolism and MAS. In a word, our findings suggest that EP exerts its cardioprotective effect on MI by regulating amino acid and energy metabolisms. Meanwhile, GC-MS-based metabolomics provided a powerful way to characterize the metabolic features of MI, with and without EP, and thereby improved our understanding of the effect and mechanisms of EP.
心肌梗死（MI）是最常见的症状，是指由于血液流向心脏的某一部分减少或停止而导致心肌损伤。电针预处理（EP）是一种最近的观察结果，已显示出诱导类似于缺血预处理的缺血耐受，表明 EP 可能是预防个体对心肌梗死易感性的一种有前途的策略。本研究通过使用气相色谱-质谱（GC-MS）-基于代谢谱的方法研究了 EP 对 MI 的作用机制。雄性 Sprague-Dawley 大鼠随机分为接受或不接受三天 PC6（内关）电针预处理。然后在第四天，每组进一步分为假手术或 MI 组，通过结扎左前降支冠状动脉诱导 MI。24h 后，采集血液样本和心脏进行后续研究。结果表明，EP 治疗显著降低了血清中 CK-MB、cTnT、AST 和 MDH 的水平，并减少了心肌梗死面积。根据 GC-MS 基于血清代谢谱分析，共鉴定出 636 个特征峰，包括 158 个已知和 478 个未知代谢物。MI 导致糖酵解相关代谢物、苹果酸-天冬氨酸穿梭（MAS）代谢物和具有抗氧化功能的嘌呤代谢物的全面代谢变化，而 EP 逆转了超过一半的差异代谢变化，主要影响氨基酸和能量代谢，特别是谷氨酸代谢和 MAS。总之，我们的研究结果表明，EP 通过调节氨基酸和能量代谢对 MI 发挥其心脏保护作用。同时，GC-MS 基于代谢组学为描述 MI 有无 EP 时的代谢特征提供了一种强大的方法，从而提高了我们对 EP 的作用和机制的理解。
