Effect and mechanism study on transcutaneous auricular vagus nerve stimulation for functional dyspepsia model rats

Objective:To explore the effect and its possible mechanism of the intervention of transcutaneous auricular vagus nerve stimulation(taVNS)for the functional dyspepsia(FD)model rats.Methods:Of the 25 male SD rats,6 rats were set as blank group,the other 19 rats were established to be the functional dyspepsia(FD)model by iodoacetamide intragastric administration,and 18 FD models were successfully established.The 18 model rats were randomly divided into a model group,a shamtaVNS group,and taVNS group,with 6 rats in each group.There was no intervention applied to the rats in the blank and model groups.Whereas,the rats in sham-taVNS group received stimulation to the rim of auricular concha of both sides,and those in taVNS group received stimulation to the cavity of auricular concha of both sides,for 30 min each time,once a day,7 days in succession.After the intervention,the gastric sensitivity of the rats in each group under different pressure conditions in the stomach,the expressions of serum brain-gut peptide motilin(MTL),cholecystokinin(CCK),glucagon-likepeptidel(GLP-1),and inflammatory factors IL-4,IL-10,and IL-1βwere detected.Results:(1)Gastric sensitivity:compared with the blank group,the gastric sensitivity of the model group was higher(P<0.05).Compared with the model group,the gastric sensitivity of the taVNS group was lower(P<0.05).Compared with the sham-taVNS group,the gastric sensitivity of the taVNS group was lower(P<0.05).(2)Expression of brain-gut peptide:compared with the blank group,MTL was lower,CCK and GLP-1 were higher in the model group(all P<0.05).Compared with the model group,MTL was higher,CCK and GLP-1 were lower in the taVNS group(all P<0.05).Compared with the shamtaVNS group,CCK and GLP-1 were lower in the taVNS group(both P<0.05).(3)Expression of inflammatory factors:compared with the blank group,IL-4 and IL-10 were lower and was higher in the model group(all P<0.05).Compared with the model group,IL-10 was higher and IL-1βwas lower in the shamtaVNS group(all P<0.05),while IL-4 and IL-10 were higher and IL-1βwas lower in the taVNS group(all P<0.05).Compared with the sham-taVNS group,IL-4 and IL-10 were higher and IL-1βwas lower in the taVNS group(all P<0.05).Conclusion:TaVNS can reduce the gastric sensitivity of FD model rats by peripheral anti-inflammatory action and regulating the abnormal secretion of brain-gut peptide.

Effects of transcutaneous auricular vagus nerve stimulation on intestinal ligandins in a rat model of functional dyspepsia

Objective:Transcutaneous auricular vagus nerve stimulation(taVNS) can relieve the symptoms of functional dyspepsia(FD) and improve the quality of life of patients,however,the mechanism underlying this effect remains unclear.Therefore,this study aimed to investigate the effects of taVNS on the expression of intestinal mucosal ligandins.Methods:This study was conducted on 24 specific Spathogen-free Sprague-Dawley rats(12 males and12 females).The rat model of FD was established by tail-clip stimulation.After FD was established successfully,all rats were randomized to either the normal group(n=6),model group(n=6),taVNS group(n=6),or sham-taVNS group(n=6).After two weeks of the respective intervention,the score of their general conditions,3 h food intake,gastric emptying rate,and the histology of gastric antrum tissues were observed to evaluate modeling success,and then the effect of taVNS was evaluated.Western blotting was used to assess the expression of the tight junction ligandins-ZO-1 and occludin-and the adhesion ligandin-β-catenin-in the duodenum.The effect of taVNs on the expression of intestinal mucosal barrier ligandins-ZO-1,occludin,and β-catenin-in FD rats was preliminarily investigated.Results:When the model-induced period was finished,the manifestations of FD in the model group rats were mental exhaustion,reduced activities,decreased score of the general conditions,and decreased3 h food intake,compared to the normal group rats.In addition,minimal eosinophil infiltration,without any mucosal erosion or ulcer,was observed in the gastric antrum mucosa.At the end of the study,the mental state of the FD rats improved,and their activities and gastric emptying rate increased in the taVNS group rats.Compared to the normal rats,the duodenal mucosa had less expression of the tight junction ligandins ZO-1 and occludin,but β-catenin expression remained unchangedin the model rats.The expression of the tight junction ligandins ZO-1 and occludin were increased in the duodenal mucosa of model rats after the taVNS intervention.Conclusion:TaVNS can improve the gastric motility and mental state of rats with FD.It may play a therapeutic role by improving the expression of the tight junction ligandin ZO-1 and occludin in the duodenal mucosa,while also repairing the duodenal mucosal barrier.