Atrial fibrillation (AF) is the most common arrhythmia in clinical practice. It has a high prevalence and poor prognosis. The application of antiarrhythmic drugs and even surgery cannot completely treat the disease, and there are many sequelae. AF can be classified into the category of "palpitation" in Chinese medicine according to its symptoms. Acupuncture has a significant effect on AF. The authors find that an important mechanism of acupuncture in AF treatment is to regulate the cardiac vagus nerve. Therefore, this article intends to review the distribution and function of vagus nerve in the heart, the application and the regulatroy effect for the treatment of AF.
Atrial Fibrillation/physiopathology* ; Humans ; Acupuncture Therapy ; Vagus Nerve/physiology* ; Animals

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; 23(4): 398-414.
Animals ; Male ; Rats, Sprague-Dawley ; STAT3 Transcription Factor/metabolism* ; alpha7 Nicotinic Acetylcholine Receptor/metabolism* ; Janus Kinase 2/metabolism* ; Atrial Fibrillation/metabolism* ; Vagus Nerve/physiopathology* ; Rats ; Acupuncture Therapy ; Signal Transduction ; Macrophages/metabolism* ; Inflammation/therapy*

Cardiovascular diseases are life-threatening illnesses with high morbidity and mortality. Suppressed vagal (parasympathetic) activity and increased sympathetic activity are involved in these diseases. Currently, pharmacological interventions primarily aim to inhibit over-excitation of sympathetic nerves, while vagal modulation has been largely neglected. Many studies have demonstrated that increased vagal activity reduces cardiovascular risk factors in both animal models and human patients. Therefore, the improvement of vagal activity may be an alternate approach for the treatment of cardiovascular diseases. However, drugs used for vagus nerve activation in cardiovascular diseases are limited in the clinic. In this review, we provide an overview of the potential drug targets for modulating vagal nerve activation, including muscarinic, and β-adrenergic receptors. In addition, vagomimetic drugs (such as choline, acetylcholine, and pyridostigmine) and the mechanism underlying their cardiovascular protective effects are also discussed.
Acetylcholine ; pharmacology ; Animals ; Cardiovascular Diseases ; drug therapy ; Cholinergic Agents ; therapeutic use ; Humans ; Receptors, Muscarinic ; drug effects ; Sympathetic Nervous System ; drug effects ; physiopathology ; Vagus Nerve ; drug effects ; physiopathology

Endoscopy plays an important role in the diagnosis and treatment of postoperative complications of gastric cancer. Endoscopic intervention can avoid the second operation and has attracted wide attention. Early gastric anastomotic bleeding after gastrectomy is the most common. With the development of technology, emergency endoscopy and endoscopic hemostasis provide a new treatment approach. According to the specific circumstances, endoscopists can choose metal clamp to stop bleeding, electrocoagulation hemostasis, local injection of epinephrine or sclerotherapy agents, and spraying specific hemostatic agents. Anastomotic fistula is a serious postoperative complication. In addition to endoscopically placing the small intestine nutrition tube for early enteral nutrition support treatment, endoscopic treatment, including stent, metal clip, OTSC, and Over-stitch suture system, can be chosen to close fistula. For anastomotic obstruction or stricture, endoscopic balloon or probe expansion and stent placement can be chosen. For esophageal anastomotic intractable obstruction after gastroesophageal surgery, radial incision of obstruction by the hook knife or IT knife, a new method named ERI, is a good choice. Bile leakage caused by bile duct injury can be treated by placing the stent or nasal bile duct. In addition, endoscopic methods are widely used as follows: abdominal abscess can be treated by the direct intervention under endoscopy; adhesive ileus can be treated by placing the catheter under the guidance of endoscopy to attract pressure; alkaline reflux gastritis can be rapidly diagnosed by endoscopy; gastric outlet obstruction mainly caused by cancer recurrence can be relieved by metal stent placement and the combination of endoscopy and X-ray can increase success rate; pyloric dysfunction and spasm caused by the vagus nerve injury during proximal gastrectomy can be treated by endoscopic pyloromyotomy, a new method named G-POEM, and the short-term outcomes are significant. Endoscopic submucosal dissection (ESD) allows complete resection of residual gastric precancerous lesions, however it should be performed by the experienced endoscopists.
Anastomosis, Surgical ; adverse effects ; Bile Ducts ; injuries ; Constriction, Pathologic ; etiology ; therapy ; Digestive System Fistula ; etiology ; therapy ; Duodenogastric Reflux ; diagnostic imaging ; etiology ; Endoscopy, Gastrointestinal ; methods ; Enteral Nutrition ; instrumentation ; methods ; Female ; Gastrectomy ; adverse effects ; Gastric Outlet Obstruction ; surgery ; Gastritis ; diagnosis ; Gastrointestinal Hemorrhage ; etiology ; therapy ; Hemostasis, Endoscopic ; methods ; Hemostatics ; administration & dosage ; therapeutic use ; Humans ; Male ; Neoplasm Recurrence, Local ; surgery ; Postoperative Complications ; diagnosis ; therapy ; Precancerous Conditions ; surgery ; Pylorus ; innervation ; physiopathology ; surgery ; Stents ; Stomach Neoplasms ; complications ; surgery ; Treatment Outcome ; Vagus Nerve Injuries ; etiology ; surgery

OBJECTIVETo explore the correlation between single acupoints used and the recurrence rate of cystitis among cystitis-prone women receiving acupuncture as a prophylactic treatment.

METHODSIn all, 58 cystitis-prone women were included in the analysis. Customised acupuncture treatments were given twice a week, over 4 weeks. The main effect parameter was the number of cystitis episodes during the 6-month observation time. Residual urine was measured at baseline, 2, 4 and 6 months using portable ultrasound equipment. Sympathetic and vagotone nerve activities were measured by using skin conductance and respiratory sinus arrhythmia, respectively.

RESULTSThe main acupoints used for patients with Kidney (Shen) qi/yang deficiency were Shenshu (BL23), Taixi (KI3), Zhongji (CV3), Sanyinjiao (SP6) and Pangguangshu (BL28), compared with Taichong (LR3), CV3, BL28, Yinlingquan (SP9) and SP6 for Liver (Gan) qi stagnation, and SP6, CV3, BL28, Zusanli (ST36) and SP9 for Spleen (Pi) qi/yang deficiency patients. The combination BL23 and KI3 were used in 16 women, 13 of which were Kidney pattern related patients. When used, the number of symptomatic episodes were reduced to a third compared with what occurred in the 42 women where this combination was not used (3/16 vs. 28/42, P<0.05). BL23 application correlated to a significant reduction in residual urine measured a few days after treatment. Patients with the pattern of Spleen qi/yang deficiency had an initial increase in residual urine after treatments.

CONCLUSIONTreating Kidney pattern related patients with the combination of BL23 and KI3 resulted in far better outcome than other points/combination of points for other Chinese medicine diagnoses. The acupoint SP6 may be less indicated than previously assumed when treating cystitis-prone women prophylactically.

Acupuncture Points ; Acupuncture Therapy ; Cystitis ; physiopathology ; prevention & control ; therapy ; urine ; Female ; Humans ; Recurrence ; Syndrome ; Urinary Tract Infections ; physiopathology ; prevention & control ; therapy ; urine ; Vagus Nerve ; physiopathology

OBJECTIVETo explore the effects of electrical stimulation at acupoints in the distribution area of auricular vagus nerve combined with sound masking on auditory brainstem response (ABR) and contents of neurotransmitters of γ-aminobutyric acid (γ-GABA), 5-hydroxytryptamine (5-HT) and acetyl choline (Ach) in inferior colliculus of tinnitus rats.

METHODSTwenty-four male adult SD rats were randomized into a control group, a model group, a 7-d treatment group and a 15-d treatment group. Except the control group, rats in the remaining groups were treated with intraperitoneal injection of 10% salicylate sodium at a dose of 350 mg/kg to establish tinnitus model. Rats in the control group were treated with injection of 0.9% NaCl. Rats in the 7-d treatment group and 15-d treatment group were treated with electrical stimulation at "Shenmen (TF₄)" and "Yidan (CO₁₁)" in the distribution area of auricular vagus nerve combined with sound masking, once a day, for 7 days and 15 days. The SigGenRP software of TDT system was applied to provide voice for single ear and collect the signal, and the voice threshold of ABR was tested. The levels of γ-GABA, 5-HT and Ach in inferior colliculus of rats were detected by enzyme linked immunosorbent assay (ELISA) and compared.

RESULTSCompared with the model group, the threshold values of ABR in 12 kHz and 16 kHz voice stimulation in the 7-d treatment group were significantly lower all P < 0.05); the threshold values of ABR from 4 kHz to 28 kHz voice stimulation in the 15-d treatment group were signally reduced (P < 0.05, P < 0.01), which was more significant than those in the 7-d treatment group. The level of γ-GABA in the model group was significantly lower than that in the control group (P < 0.05), and that in the 15-d treatment group was apparently higher than that in the model group (P < 0.05). The level of 5-HT in the model group was markedly higher than that in the control group (P < 0.05), and that in the 7-d treatment group was lower than that in the model group (P < 0.05), while that in the 15-d treatment group was apparently higher than that in the model group (P < 0.05). The level of Ach in the model group was obviously; lower than that in the control group (P < 0.05), and that in the 7-d treatment group was higher than that in the model group (P < 0.05).

CONCLUSIONElectrical stimulation at auricular vagus nerve combined with sound masking) could regulate the threshold of ABR, especially in the 15-d treatment group. This may be ascribed to modulating the levels of neurotransmitter of γ-GABA, 5-HT and Ach in inferior colliculus.

Acupuncture Points ; Animals ; Brain Stem ; physiopathology ; Electric Stimulation ; Evoked Potentials, Auditory, Brain Stem ; Humans ; Inferior Colliculi ; physiopathology ; Male ; Neurotransmitter Agents ; metabolism ; Rats ; Rats, Sprague-Dawley ; Serotonin ; metabolism ; Tinnitus ; physiopathology ; therapy ; Vagus Nerve ; physiopathology ; gamma-Aminobutyric Acid ; metabolism

OBJECTIVETo observe abnormalities in heart rate variability (HRV) in diabetic rats and to explore the effects of treatment with Guizhi Decoction ([symbols; see text]) on cardiac autonomic nervous (CAN) imbalance.

METHODSA radio-telemetry system for monitoring physiological parameters was implanted into rats to record electrocardiac signals and all indictors of HRV [time domain measures: standard deviation of all RR intervals in 24 h (SDNN), root mean square of successive differences (RMSSD), percentage of differences between adjacent RR intervals greater than 50 ms (PNN50), and standard deviation of the averages of RR intervals (SDANN); frequency domain measures: low frequency (LF), high frequency (HF), total power (TP), and LF/HF ratio]. The normal group was randomly selected, and the remaining rats were used to establish streptozocin (STZ)-induced diabetic model. After 4 weeks, the model rats were divided into the model group, the methycobal group, and the Guizhi Decoction group, 9 rats in each group. Four weeks after intragastric administration of the corresponding drugs, the right atria of the rats were collected for immunohistochemical staining of tyrosine hydroxylase (TH) and choline acetyltransferase (CHAT) to observe the distribution of the sympathetic and vagus nerves in the right atrium. The myocardial homogenate from the interventricular septum and the left ventricle was used for determination of TH, CHAT, growth-associated protein 43 (GAP-43), nerve growth factor (NGF), and ciliary neurotrophic factor (CNTF) levels using an enzyme-linked immunosorbent assay.

RESULTS(1) STZ rats had elevated blood glucose levels, reduced body weight, and decreased heart rate; there was no difference between the model group and the drug treated groups. (2) Compared with the model group, only RMSSD and TP increased in the methycobal group significantly (P<0.05); SDNN, RMSSD, PNN50, LF, HF, and TP increased, LF/HF decreased (P<0.05), and SDANN just showed a decreasing trend in the Guizhi Decoction group (P>0.05). TH increased, CHAT decreased, and TH/CHAT increased in the myocardial homogenate of the model group (P<0.05). Compared with the model group, left ventricular TH reduced in the methycobal group; and in the Guizhi Decoction group CHAT increased, while TH and TH/CHAT decreased (P<0.05). Compared with the model group, CNTF in the interventricular septum increased in the methycobal group (P<0.05); GAP-43 increased, NGF decreased, and CNTF increased (P<0.05) in the Guizhi Decoction group. There were significant differences in the reduction of NGF and elevation of CNTF between the Guizhi Decoction group and the methycobal group (P<0.05). (3) Immunohistochemical results showed that TH expression significantly increased and CHAT expression significantly decreased in the myocardia of the model group, whereas TH expression decreased and CHAT expression increased in the Guizhi Decoction group (P<0.05).

CONCLUSIONGuizhi Decoction was effective in improving the function of the vagus nerve, and it could alleviate autonomic nerve damage.

Animals ; Autonomic Nervous System ; drug effects ; physiopathology ; Choline O-Acetyltransferase ; metabolism ; Diabetes Mellitus, Experimental ; drug therapy ; physiopathology ; Diabetic Neuropathies ; drug therapy ; physiopathology ; Disease Models, Animal ; Drugs, Chinese Herbal ; pharmacology ; Heart ; innervation ; physiopathology ; Heart Rate ; drug effects ; physiology ; Male ; Monitoring, Physiologic ; methods ; Rats, Wistar ; Telemetry ; methods ; Treatment Outcome ; Tyrosine 3-Monooxygenase ; metabolism ; Vagus Nerve ; drug effects ; physiopathology

OBJECTIVETo compare the patterns of respiratory function variations resulting from the classical reflex of blood pressure fall and high blood levels of bile acid, so as to provide evidence for the regulation of respiratory function via bile acids.

METHODSSeventy New Zealand male Rabbits, under general anesthesia with 20% urethane, were subjected to tracheal intubations and carotid artery cannulations via median incisions of the neck. Using a biological signal acquisition system, the changes in the breathing and blood pressure were observed in response to stimulation of the pneumogastric nerves or to ear vein injections of diluted bile acids or the water solutions of 5 dissociated bile acids.

RESULTSStimulation of the pneumogastric nerves and injections of diluted bile acids both lowered the blood pressure without significant differences in the total reaction time (T). However, the total respiratory reaction time of bile acids, RT(bile acids), was 9-10 times longer than the total reaction time of blood pressure T(bile acids) (P<0.001). The peak-peak values of respiratory range RR(bile acids) were higher than that RR(pneumogastric nerves)resulting from the classical reflex (P<0.001). In the interval of RT1(bile acids), the values of RR(bile acids) were significantly higher than those of RR(bile acids) in RT2(bile acids) interval. UDCA produced no significant influence on blood pressure or respiratory function (P<0.05) as the other 4 dissociated bile acid reagents did (P<0.001).

CONCLUSIONHigh blood levels of bile acids not only act through reflex factors but also have direct effects on respiratory function regulation. Under our experimental conditions, UDCA has no effect on blood pressure or respiratory function, but the other 4 dissociated bile acid reagents can all dose-dependently lower blood pressure and significantly affect respiratory function.

Animals ; Bile Acids and Salts ; blood ; Blood Pressure ; Male ; Rabbits ; Reflex ; Respiratory Function Tests ; Vagus Nerve ; physiopathology

Adolescent ; Autonomic Nervous System ; physiopathology ; Blood Pressure ; physiology ; Blood Pressure Monitoring, Ambulatory ; methods ; Child ; Child, Preschool ; Circadian Rhythm ; Female ; Heart Rate ; physiology ; Humans ; Male ; Posture ; physiology ; Syncope, Vasovagal ; diagnosis ; etiology ; physiopathology ; Tilt-Table Test ; Vagus Nerve ; physiopathology

OBJECTIVETo investigate the retrograde changes in the dorsal motor nuclei (DMV) of the vagus nerve after vagotomy in rats.

METHODSNissl staining and immunohistochemistry were used to observe the morphological and quantitative changes of the DMV and alterations of the expression of iNOS and NADPH after severing of the vagus nerve in adult male Wistar rats.

RESULTSCompared with the control group, the rats with right vagotomy showed obvious morphological changes and a significantly decreased number of neurons in the right DMV (P<0.05). Numerous iNOS- and NADPH-immunopositive cells were detected in the right DMV 5 and 10 days after right vagotomy.

CONCLUSIONVagotomy causes obvious retrograde changes in rat DMV shown by a significantly decreased number and obvious morphological changes of the neurons in the DMV.

Animals ; Male ; NADP ; metabolism ; Neurons ; metabolism ; Nitric Oxide Synthase Type II ; metabolism ; Rats ; Rats, Sprague-Dawley ; Vagotomy ; Vagus Nerve ; pathology ; physiopathology ; surgery