Establishment Of Non-erosive Gastroesophageal Reflux Disease Syndrome Combined With Rat Model And Mechanism Of Intervention Effect Of Shuganheweifang

Objective:To superimpose psychological stress intervention in the model of gastroesophageal reflux disease,combining Western medicine with traditional Chinese medicine liver stagnation syndrome,to establish and evaluate rat model of non-erosive gastroesophageal reflux disease syndrome;to study the effect of the prescription on a rat model of non-erosive gastroesophageal reflux disease with psychological impairment.Methods:The rat model of gastroesophageal reflux disease was replicated by pylorus of half-ligation combined with cardia tearing.After one week,the forced swimming test,restraint test,fasting,water ban and other psychological stress methods were added on the basis of the reflux model.Continuous intervention for two weeks,the model is evaluated by means of changes in esophageal microenvironment such as esophageal cell gap,inflammatory factor expression,rat behavior,and hypothalamic-pituitary-adrenergic axis(HPA axis)related protein.On this basis,we observed the intervention effect of Shugan Hewei Recipe in this model,and the regulation of Shuganhewei Recipe on the combination of CRF signaling pathway-related genes and GABAergic neurons related genes in rat hypothalamus.To explore the central effect of Shuganhewei Recipe on rats with disease syndrome.Results:1.There was no erosion of the esophageal mucosa in the rat model combined with the disease;The p H value decreased,compared with the sham operation group,the difference was statistically significant(P=0.002).Compared with the liver stagnation group,the difference was statistically significant.(P<0.001).However,there were changes in the esophageal microenvironment in the rats with syndrome combination,including:1 papillary hyperplasia of the lower esophagus,thickening of the basal layer;2 decreased expression of DSG1 mRNA between mucosal epithelial cells,compared with sham surgery Statistically significant(P<0.001),the difference was statistically significant compared with the reflux group(P=0.003);Cell gap widening,compared with the sham operation group,the difference was statistically significant(P<0.001);3Compared with the reflux group,the expression of IL-1?mRNA and IL-6 mRNA in the lower esophageal mucosa decreased(P<0.05),and the content of IL-4 and IL-10 in peripheral blood increased(P<0.05).Rats have a shift in the balance between pro-inflammatory and anti-inflammatory;2.There are certain behavioral changes in the syndrome-binding group,including:1 the preference for syrup is reduced,compared with the sham-operated group,the difference is statistically significant(P=0.001),compared with the reflux group,the difference was statistically significant(P=0.012);2In the syndrome group,the number of crawling cells and the number of erects in the open field experiment were significantly reduced,compared with the sham operation group,the difference was statistically significant(P<0.05);The number of modifications was significantly increased,compared with the sham operation group,the difference was statistically significant(P<0.05).The rats in the combination group had the longest resting time in forced swimming,compared with the sham operation group and the reflux group,the difference was statistically significant(P<0.001);3.Compared with the sham operation group,the protein content of CRH,ACTH and CORT in the peripheral blood of the syndrome group were significantly increased,the difference was statistically significant(P<0.05);Compared with the sham operation group,the expressions of CRF,CRF1,CRF2,PKA,GABA_Aand GABA_BmRNA in the hypothalamus of the rats in the syndrome group were significantly decreased,and the difference was statistically significant(P<0.05).5.Shugan and stomach of intervention effects were as follows:1 Compared with the combination of disease and syndrome,the prolonged esophageal mucosal epithelial nipple was not significantly prolonged,and the basal layer was thickened;2 Compared with the syndrome group,the expression of DSG1 mRNA in Shuganheweifang group was up-regulated in the submucosal epithelial cells(P=0.0018),and the cell gap in Shugan and Weifang group was significantly shortened(P=0.002).3 Compared with the syndrome-combined group,the Shugan and Stomach groups were down-regulated.The expression of IL-1?mRNA and IL-6 mRNA in the lower esophagus and the decrease of IL-4 in peripheral blood and the content of IL-10,but the difference was not statistically significant,compared with the combination of disease and syndrome;4 Shugan and Shoufang can improve the preference of sucrose in rats with syndrome combination,and the combination with disease syndrome,the ratio was statistically significant(P<0.001).In the Shuchang and Weifang group,the number of crawling cells and the number of erects were increased significantly in the open field experiment,and the number of modifications was significantly reduced.However,compared with the syndrome-combined group,the difference was not statistical.The significance of learning;the static time of rats in Shuganhewei group was significantly shortened in forced swimming,compared with the syndrome group,the difference was statistically significant(P<0.001);5 Compared with the syndrome group,Shuganhewei recipe can reduce the protein content of CRH in peripheral blood,but the difference is not statistically significant;It can reduce the content of ACTH and CORT in peripheral blood,the difference was statistically significant(P<0.05);Compared with the group of disease syndrome,the expression levels of CRF,CRF1,CRF2,GABA_Aand GABA_BmRNA in hypothalamus were up-regulated(P<0.05).Shuganhewei recipe can up-regulate the expression levels of PKAa mRNA in hypothalamus.,but the difference was not statistically significant.Conclusion:1.The combination of disease syndrome rat model is more suitable for non-erosive gastroesophageal reflux disease.It is an ideal animal model of non-erosive gastroesophageal reflux disease with psychological disorder.2.In this model,we hypothesized that Shuganhewei recipe has the effects of improving the esophageal microenvironment,alleviating anxiety and depression,restoring the peripheral function of HPA axis balance,and regulating the multi-target effect of the central nervous system.