Objectives: To observe the effect of electroacupuncture (EA) at "Zusanli" (ST36) on improving cardiac function in mice with chronic heart failure (CHF), so as to explore the mechanism of its regulation on the autonomic nervous system.
Methods: Eighteen C57BL/6J mice were randomly divided into sham-surgery, model, and EA groups, with 6 mice in each group. The model of myocardial ischemia followed by CHF was induced by ligation of the anterior descending branch of the left coronary artery. Two weeks after modeling surgery, EA intervention (0.5 mA, 2 Hz/15 Hz) was performed bilaterally at ST36 in the EA group, 20 min each time, once every other day for 4 weeks. The left ventricular ejection fraction (LVEF), left ventricular fractional shortening (LVFS), left ventricular end-systolic diameter (LVESD), left ventricular end-systolic volume (LVESV), left ventricular end-diastolic diameter (LVEDD), and left ventricular end-diastolic volume (LVEDV) were evaluated using echocardiographic imaging. The exercise tolerance was observed in an exhaustive test. Electrocardiograms were recorded using an electrophysiological recording system to analyze heart rate (HR) changes before and after EA, and frequency domain analysis was used to analyze the heart rate variability (HRV), including low-frequency (LF) component, high-frequency (HF) component, and their ratio (LF/HF). Immunofluorescence was used to observe the number of choline acetyltransferase (ChAT)+/c-fos+ co-labeled neurons in the dorsal motor nucleus of the vagus (DMV).
Results: In terms of cardiac function, compared with the sham-surgery group, the LVEF and LVFS were decreased (P<0.001) and the LVESD, LVEDD, LVESV, and LVEDV were increased (P<0.001, P<0.01) two weeks after modeling of mice in the model group. After 2 weeks of EA intervention, the LVESD and LVESV in the EA group were significantly smaller than those in the model group (P<0.05). After 4 weeks of intervention, the LVEF and LVFS in the EA group were significantly higher than those in the model group (P<0.05), and the LVESD and LVESV were significantly reduced (P<0.05, P<0.01). Compared with the model group, EA significantly improved the exercise tolerance of CHF mice (P<0.05). Compared with the sham-surgery group, the LF/HF in the model group and EA group were significantly increased (P<0.05) 2 weeks after modeling, indicating autonomic imbalance. After 4 weeks of intervention, the LF/HF in the EA group showed lower trend than that in the model group but the difference was not statistically significant. Additionally, after immediate EA, HR decreased (P<0.05, P<0.01), HF increased (P<0.01), and both LF and LF/HF decreased significantly (P<0.05) of mice in the EA group, indicating that EA corrected the autonomic imbalance in CHF mice. The number of ChAT+/c-fos+ co-labeled neurons in the DMV of the EA group was significantly higher (P<0.001) than that in the model group.
Conclusions: EA at ST36 significantly improved cardiac function and exercise tolerance in CHF mice. The underlying mechanism may be related to the activation of vagus efferent nerve and the regulation of autonomic nerve balance.
目的: 观察电针“足三里”对慢性心力衰竭（CHF）小鼠心功能的改善作用并初步探讨其调节自主神经的作用机制。方法: C57BL/6J小鼠随机分为假手术组、模型组、电针组，每组6只。采用左冠状动脉前降支结扎的方法制备心肌缺血后CHF小鼠模型。在造模手术2周后对电针组小鼠双侧“足三里”行电针干预，每次20 min，隔日1次，干预4周。采用小动物超声成像技术检测左室射血分数（LVEF）、左室短轴缩短率（LVFS）、左室收缩末期内径（LVESD）、左室收缩末期容积（LVESV）、左室舒张末期内径（LVEDD）、左室舒张末期容积（LVEDV）；力竭实验观察各组小鼠运动耐量；电生理记录系统记录心电图，分析电针前后心率（HR）变化，并采用频域分析法分析心率变异性（HRV）中低频（LF）成分、高频（HF）成分及其比值（LF/HF）变化；免疫荧光法观察迷走神经背核（DMV）中乙酰胆碱转移酶（ChAT）+/c-fos+共标神经元数量。结果: 心功能方面，与假手术组比较，造模后，模型组小鼠LVEF、LVFS显著降低（P<0.001），LVESD、LVEDD、LVESV、LVEDV显著增大（P<0.001，P<0.01）。电针干预2周后，电针组LVESD、LVESV较模型组显著减小（P<0.05）；电针干预4周后，电针组LVEF、LVFS较模型组显著升高（P<0.05），LVESD、LVESV显著减小（P<0.05，P<0.01）。与模型组比较，电针可以显著提高CHF小鼠的运动耐量（P<0.05）。与假手术组比较，造模2周后模型组和电针组小鼠LF/HF显著升高（P<0.05），自主神经失衡；经过4周干预后，模型组小鼠LF/HF仍升高（P<0.05），电针组小鼠LF/HF较模型组有降低趋势但差异无统计学意义。电针组小鼠即刻电针后HR降低（P<0.05，P<0.01），HF升高（P<0.01），LF和LF/HF均显著降低（P<0.05），即电针纠正了CHF小鼠的自主神经失衡。电针组DMV中ChAT+/c-fos+共标神经元数量较模型组明显增多（P<0.001）。结论: 电针“足三里”能够显著改善CHF小鼠心功能，提高运动耐量，其机制可能与激活迷走传出神经，调节自主神经平衡有关。.
Keywords: Chronic heart failure; Electroacupuncture; Vagus nerve; “Zusanli” (ST36).