Electroacupuncture Preconditioning Attenuates Myocardial Ischemia-Reperfusion Injury by Inhibiting Microglial Engulfment of Dendritic Spines in the Fastigial Nucleus

A major side effect of reperfusion therapy following myocardial infarction is myocardial ischemia-reperfusion injury (MIRI). Electroacupuncture preconditioning (EA-pre) has a long history in the treatment of cardiovascular diseases. Here, we demonstrate how EA-pre attenuates MIRI by affecting the phagocytosis of neuronal dendritic spines of microglia of the fastigial nucleus (FNmicroglia). From optical-fiber-based Ca2+ signal recordings in GABAergic neurons of the FN (FNGABA), we observed that EA-pre for 7 days increased activity in FNGABA and then improved myocardial injury by inhibiting abnormal activities of glutaminergic neurons of the FN (FNGlu) during MIRI. Interestingly, we observed changes in the quantity and shape of FN microglia in mice treated with EA-pre, and a decrease in the phagocytosis of FNGABA neuronal dendritic spines by microglia. Furthermore, the effects of improving MIRI were reversed when EA-pre mice were chemically activated by intra-FN lipopolysaccharide injection, followed by a reduction in FNGABA activity. Overall, our results provide new insight indicating that EA-pre negatively regulates microglial engulfment capacity, thus promoting the improvement of cardiac sympathetic nervous injury and disorders during MIRI.心肌梗死患者接受再灌注治疗后的主要不良反应为心肌缺血再灌注损伤（MIRI）。电针预处理（EA-pre）在心血管疾病治疗中已有悠久应用历史。本研究阐明了电针预处理（EA-pre）通过调控小脑顶核小胶质细胞（FNmicroglia）对神经元树突棘的吞噬作用，从而减轻MIRI的具体机制。通过对小脑顶核γ-氨基丁酸能神经元（FNGABA）开展基于光纤的钙离子信号记录，我们发现7天的EA-pre可增强FNGABA的活性，并通过抑制MIRI过程中小脑顶核谷氨酸能神经元（FNGlu）的异常活动，进而改善心肌损伤。值得注意的是，我们观察到接受EA-pre干预的小鼠其小脑顶核小胶质细胞的数量与形态发生改变，且小胶质细胞对FNGABA神经元树突棘的吞噬作用减弱。此外，若对EA-pre预处理的小鼠通过小脑顶核内注射脂多糖进行化学激活，可逆转其对MIRI的改善作用，并伴随FNGABA活性降低。综上，本研究结果揭示了新的机制：EA-pre可负向调控小胶质细胞的吞噬能力，进而改善MIRI过程中的心脏交感神经损伤与功能紊乱。