Background: Myocardial ischemia–reperfusion can further exacerbate myocardial injury and increase the risk of death. Our previous research found that the paraventricular nucleus (PVN) of the hypothalamus plays a crucial role in the improvement of myocardial ischemia–reperfusion injury (MIRI) by electroacupuncture (EA) pretreatment, but its mechanism of action is still unclear. CRH neurons exhibit periodic concentrated expression in PVN, but further research is needed to determine whether they are involved in the improvement of MIRI by EA pretreatment. Meanwhile, numerous studies have shown that changes in sympathetic nervous system innervation and activity are associated with many heart diseases. This study aims to investigate whether EA pretreatment improves MIRI through sympathetic nervous system mediated by PVN^CRHneurons.Methods: Integrated use of fiber-optic recording, chemical genetics and other methods to detect relevant indicators: ECG signals were acquired through Powerlab standard II leads, and LabChart 8 calculated heart rate, ST-segment offset, and heart rate variability (HRV); Left ventricular ejection fraction (LVEF), left ventricular short-axis shortening (LVFS), left ventricular end-systolic internal diameter (LVIDs) and interventricular septal thickness (IVSs) were measured by echocardiography; Myocardial infarct area (IA) and area at risk (AAR) were calculated by Evans-TTC staining. Pathological changes in cardiomyocytes were observed by HE staining; Changes in PVN^CRHneuronal activity were recorded by fiber-optic photometry; Sympathetic nerve discharges were recorded for in vivo electrophysiology; NE and TH protein expression was assayed by Western blot.Results: Our data indicated that EA pretreatment can effectively alleviate MIRI. Meanwhile, we found that in the MIRI model, the number and activity of CRH neurons co labeled with c-Fos in the PVN area of the rat brain increased, and the frequency of sympathetic nerve discharge increased. EA pretreatment could reverse this change. In addition, the results of chemical genetics indicated that inhibiting PVN^CRHneurons has a similar protective effect on MIRI as EA pretreatment, and the activation of PVN^CRHneurons can counteract this protective effect.Conclusion: EA pretreatment can inhibit PVN^CRHneurons and improve MIRI by inhibiting sympathetic nerve, which offers fresh perspectives on the application of acupuncture in the management of cardiovascular disease.

Cardiovascular disease is the leading cause of death worldwide. As a traditional Chinese treatment method, acupuncture has a unique role in restoring the balance of the human body environment. Due to its safety, non-invasive nature, and effectiveness in treating cardiovascular diseases, acupuncture has been widely welcomed and recognized among the world. A large amount of evidence shows that acupuncture can effectively regulate cardiovascular diseases through the autonomic nervous system. The hypothalamus, as an important component of regulating the autonomic nervous system, plays an important role in regulating the internal environment, maintaining homeostasis, and preserving physiological balance. However, there is currently a scarcity of review articles on acupuncture signal transduction and acupuncture improving cardiovascular disease through the hypothalamus and autonomic nervous system. This review delves into the transduction of acupuncture signals and their neural regulatory mechanisms on the hypothalamus and autonomic nervous system, elucidating their impact on cardiovascular disease. Review the basic and clinical studies on acupuncture signal transduction mechanisms and the role of the hypothalamus and ANS in acupuncture treatment of cardiovascular diseases published in four English databases (PubMed, Web of Science, MEDLINE, and Springer Cochrane Library) and two Chinese databases (Wanfang Database and China National Knowledge Infrastructure Database) over the past 20 years. Through sensory stimulation, acupuncture effectively transmits signals from the periphery to the hypothalamus, where they are integrated, and finally regulate the autonomic nervous system to treat cardiovascular diseases. Acupuncture exhibits significant potential as a therapeutic modality for cardiovascular diseases by orchestrating autonomic nervous system regulation via the hypothalamus, thereby gifting novel perspectives and methodologies for the prevention and treatment of cardiovascular ailments.

Qing Yu, Li-bin Wu, Fan Zhang, Xiao-tong Wei, Pian-pian Chen, Shuai-ya Wang, Mei-yi Cai, Qi Shu, Liao-yuan Li, Zi-jian Wu, Rong-lin Cai, Ling Hu. J Acupunct Meridian Stud 2021;14:207-18. https://doi.org/10.51507/j.jams.2021.14.6.207

Aim: The occurrence of myocardial ischemia–reperfusion injury (MIRI) is accompanied by neuroinflammatory reactions and is closely related to the overactivation of microglia. Currently, effective clinical strategies to prevent MIRI are unclear. This study investigated potential therapeutic targets and the mechanisms of electroacupuncture pretreatment (EA‐pre) for MIRI. Methods: A MIRI mouse model was established by ligating the left anterior descending branch of the heart for 30 min and reperfusion for 2 h. The mechanisms by which EA‐pre alleviates MIRI were investigated through immunofluorescence staining, chemogenetics, and fiber photometry recordings, focusing on the potential involvement of microglia and glutamate (Glu) neurons in the lateral hypothalamic (LH). Results: EA‐pre improves cardiac function in MIRI mice by suppressing microglial activation in the LH. The underlying mechanism likely involves EA‐pre inhibition of microglial engulfment of inhibitory synapses around LH ^Glu neurons. Targeted activation of LH ^microglia reverses EA's inhibitory effect, thereby increasing LH ^Glu neuronal activity and triggering overactivation of the sympathetic nervous system (SNS), which ultimately exacerbates MIRI. Conclusion: EA‐pre inhibits microglial engulfment of inhibitory synapses around LH ^Glu neurons in MIRI mice, thereby suppressing LH ^Glu neuronal activity, reducing SNS output, and ultimately exerting cardioprotective effects.

Background: Electroacupuncture pretreatment (EA-pre) has been shown to help reduce myocardial ischemia-reperfusion injury (MIRI), but the underlying mechanism remains unclear. Our previous studies indicated that EA activates the cerebellar cortex, specifically the Crus Ⅰ. However, whether activation of the Crus Ⅰ contributes to the attenuation of MIRI induced by EA-pre remains unclear. This study investigated the possible relationship between EA-induced relief of MIRI and the activation of Crus Ⅰ. Methods: Electrocardiogram recording, echocardiography, and cardiac histology staining were used to assess the heart’s functional status. In vivo electrophysiological recordings, Fos-targeted recombination in active populations (Fos-TRAP) gene-labeling technology and chemogenetic viral modulation were used to explore the effects of Crus Ⅰ activation in EA-pre on MIRI. Results: In vivo electrophysiological recordings demonstrated that Crus Ⅰ plays a crucial role in EA-pre by modulating sympathetic activity to alleviate MIRI. Subsequent Fos-TRAP studies showed that EA stimulation primarily induces changes in the neuronal activity of Crus Ⅰ Purkinje cells (Crus ⅠPC). Chemogenetic viral manipulations further verified that EA-pre suppresses PC activity in MIRI. Conclusion: EA-pre mitigated cardiac sympathetic nerve dysfunction during MIRI by regulating Crus ⅠPC activity.