Cholinergic neurons in the dorsal nucleus of the vagus nerve are involved in the mechanism of action of electroacupuncture at HT7 in a mouse model of chronic heart failure.

OBJECTIVE

To investigate the role and mechanism of the dorsal motor nucleus of the vagus nerve (DMV) in the effects of electroacupuncture (EA) at HT7 in a mouse model of chronic heart failure (CHF).

METHODS

A CHF model was established in male C57 mice by ligating the anterior descended branch of the left coronary artery. In part I of the experiment, mice were randomly divided into Control, untreated model (CHF) and EA-treated model (CHF + EA) groups (n = 6 each). In part II, mice were randomly divided into the following groups (n = 6 each): EA-treated model group (CHF + EA); EA-treated model group receiving cholinergic neuron promoter chemogenetic activating virus encoding human M4 muscarinic (hM4) receptor (hM4D) and clozapine-N-oxide (CNO) (CHF + hM4D + CNO + EA); EA-treated model group additionally receiving "empty" virus encoding enhanced green fluorescence protein (EGFP) and CNO (CHF + EFGP + CNO + EA); EA-treated model group receiving hM4D only (CHF + hM4D + EA); and EA-treated model group receiving CNO only (CHF + CNO + EA). All mice except those in the Control and CHF groups were treated with bilateral EA at HT7 (frequency 2 Hz, intensity 2mA, pulse width 0.2 ms ± 20%) once a day (20 min each time) for 7 days. Left ventricular ejection fraction (LVEF), left ventricular fractional shortening (LVFS), scar area and serum inflammatory factor levels were evaluated using a Doppler ultrasound imaging system, Masson staining, ELISA and other methods.

RESULTS

Compared with the Control group, LVEF/LVFS in the CHF group decreased (p < 0.001), the scar area was larger, atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP) and interleukin (IL)-6 levels increased significantly, and acetylcholine (ACh) decreased significantly (p < 0.001) in the CHF group. Compared with the CHF group, LVEF/LVFS increased (p < 0.001), scar area was smaller, ANP, BNP and IL-6 decreased significantly and ACh increased significantly (p < 0.001) in the CHF + EA group. Compared with the CHF + EA group, the CHF + hM4D + CNO + EA group exhibited a decrease in LVEF/LVFS (p < 0.001), a larger scar area, a significant increase in ANP, BNP and IL-6, and a significant decrease in ACh (p < 0.001),while there was no significant difference in each index between the CHF + CNO + EA and CHF + hM4D + EA groups (p > 0.05). Compared with the CHF + hM4D + CNO + EA group, the CHF + EGFP + CNO + EA exhibited an increase in LVEF/LVFS (p < 0.001), a smaller scar area, a significant decrease in ANP, BNP and IL-6, and a significant increase in ACh (p < 0.001).

CONCLUSION

Electroacupuncture at (HT7) may activate DMVAch and reduce myocardial fibrosis, thereby improving CHF, in a mouse model.