针刺通过α7烟碱型乙酰胆碱受体-JAK2/STAT3通路激活迷走神经-巨噬细胞轴,改善心房颤动大鼠的心脏电生理和炎症反应。
Acupuncture activates vagus nerve-macrophage axis and improves cardiac electrophysiology and inflammatory response in rats with atrial fibrillation via α7nAChR-JAK2/STAT3 pathway.
作者信息
Li Zhi-Han, Yang Wen-Min, Huang Qi, Shi Guang-Xia, Liu Cun-Zhi, Zhang Yu-Qin
机构信息
School of Acupuncture-Moxibustion and Tuina, Beijing University of Chinese Medicine, Beijing 100029, China; International Acupuncture and Moxibustion Innovation Institute, Beijing University of Chinese Medicine, Beijing 100029, China.
School of Acupuncture-Moxibustion and Tuina, Beijing University of Chinese Medicine, Beijing 100029, China.
出版信息
J Integr Med. 2025 Jun 13. doi: 10.1016/j.joim.2025.06.002.
OBJECTIVE
The occurrence and development of atrial fibrillation (AF) are influenced by the autonomic nervous system and inflammation. Acupuncture is an effective treatment for AF. This study explored the protective effects of acupuncture in a rat model of paroxysmal AF and investigated its mechanisms.
METHODS
Male Sprague-Dawley rats (n = 130) were randomly divided into blank control (Con), sham operation (Sham), AF, and acupuncture treatment (Acu) groups. A paroxysmal AF model was established by rapid atrial pacing through the jugular vein. Rats in the Acu group were immobilized to receive acupuncture treatment at Neiguan acupoint (PC6) for 20 min daily for seven days. The other groups were immobilized for the same duration over the treatment period but did not receive acupuncture. The AF induction rate, AF duration, cardiac electrophysiological parameters, and heart rate variability were evaluated by monitoring surface electrocardiogram and vagus nerve discharge signals. After the intervention, the rats were euthanized, and atrial morphology was assessed using haematoxylin and eosin staining. The expression of macrophage F4/80 antigen (F4/80) and cluster of differentiation (CD) 86 in atrial myocardial tissue was detected using immunohistochemistry, immunofluorescence and flow cytometry. The expression levels or contents of interleukin (IL)-1β, IL-6, tumor necrosis factor-α (TNF-α), α7 nicotinic acetylcholine receptor (α7nAChR), phosphorylated Janus kinase 2 (p-JAK2), and phosphorylated signal transducer and activator of transcription 3 (p-STAT3) in atrial myocardial tissue were detected using Western blotting, reverse transcription-quantitative polymerase chain reaction, or enzyme-linked immunosorbent assay. The role of α7nAChR in acupuncture treatment was verified by intraperitoneal injection of the α7nAChR antagonist methyllycaconitine (MLA).
RESULTS
Compared with the AF group, acupuncture significantly reduced AF duration and induction rate, improved cardiac electrophysiology by enhancing vagus nerve activity and regulating autonomic balance. It also decreased the pro-inflammatory M1 macrophage proportion, alleviating myocardial injury and infiltration. MLA weakened acupuncture's electrophysiological improvement and anti-inflammatory effect. Results suggest that acupuncture triggers the α7nAChR-JAK2/STAT3 pathway and exerts cardioprotection via neuroimmune regulation.
CONCLUSION
Acupuncture significantly reduced the AF induction rate, shortened AF duration, improved cardiac electrophysiological parameters, enhanced vagus nerve activity, and decreased the expression of pro-inflammatory M1 macrophages and inflammatory factors in rats with paroxysmal AF. Its positive effects are related to the activation of the α7nAChR-mediated JAK2/STAT3 signalling pathway, indicating that the interaction between cardiac vagus nerve and macrophages may be a potential target for acupuncture in the prevention and treatment of AF. Please cite this article as: Li ZH, Yang WM, Huang Q, Shi GX, Liu CZ, Zhang YQ. Acupuncture activates vagus nerve-macrophage axis and improves cardiac electrophysiology and inflammatory response in rats with atrial fibrillation via α7nAChR-JAK2/STAT3 pathway. J Integr Med. 2025; Epub ahead of print.
目的
心房颤动(AF)的发生发展受自主神经系统和炎症影响。针刺是治疗AF的一种有效方法。本研究探讨针刺对阵发性AF大鼠模型的保护作用并研究其机制。
方法
将130只雄性Sprague-Dawley大鼠随机分为空白对照组(Con)、假手术组(Sham)、AF组和针刺治疗组(Acu)。通过颈静脉快速心房起搏建立阵发性AF模型。Acu组大鼠固定后每日于内关穴(PC6)接受针刺治疗20分钟,共7天。其他组在治疗期间固定相同时间但不接受针刺。通过监测体表心电图和迷走神经放电信号评估AF诱发率、AF持续时间、心脏电生理参数和心率变异性。干预后,将大鼠安乐死,用苏木精-伊红染色评估心房形态。采用免疫组织化学、免疫荧光和流式细胞术检测心房心肌组织中巨噬细胞F4/80抗原(F4/80)和分化簇(CD)86的表达。采用蛋白质印迹法、逆转录-定量聚合酶链反应或酶联免疫吸附测定法检测心房心肌组织中白细胞介素(IL)-1β、IL-6、肿瘤坏死因子-α(TNF-α)、α7烟碱型乙酰胆碱受体(α7nAChR)、磷酸化Janus激酶2(p-JAK2)和磷酸化信号转导子及转录激活子3(p-STAT3)的表达水平或含量。通过腹腔注射α7nAChR拮抗剂甲基lycaconitine(MLA)验证α7nAChR在针刺治疗中的作用。
结果
与AF组相比,针刺显著缩短AF持续时间和诱发率,通过增强迷走神经活性和调节自主神经平衡改善心脏电生理。还降低促炎M1巨噬细胞比例,减轻心肌损伤和浸润。MLA减弱针刺的电生理改善作用和抗炎作用。结果表明针刺触发α7nAChR-JAK2/STAT3通路并通过神经免疫调节发挥心脏保护作用。
结论
针刺显著降低阵发性AF大鼠的AF诱发率,缩短AF持续时间,改善心脏电生理参数,增强迷走神经活性,降低促炎M1巨噬细胞和炎症因子的表达。其积极作用与α7nAChR介导的JAK2/STAT3信号通路激活有关,表明心脏迷走神经与巨噬细胞之间的相互作用可能是针刺防治AF的潜在靶点。请引用本文:Li ZH, Yang WM, Huang Q, Shi GX, Liu CZ, Zhang YQ. 针刺通过α7nAChR-JAK2/STAT3通路激活迷走神经-巨噬细胞轴并改善心房颤动大鼠的心脏电生理和炎症反应。《整合医学杂志》。2025年;提前在线发表。