| Objective :To study the changes of Ghrelin/GHS-R1 pathway in the rat model of gastroesophageal reflux disease combined with the live-gastric disharmony syndrome,and took the Ghrelin/GHS-R1 pathway as a starting point to clarify the mechanism of Tongjiang granule in improving liver-stomach disharmony syndrome of gastroesophageal reflux disease,and clarify the intervention effect of drugs.Methods : This subject consists of two parts of experiments.Experiment1:55 SD rats were randomly divided into blank group(n=11),sham operation group(n=11),disease model group(n=11),syndrome model group(n=11)and disease-syndrome combined model group(n=11).GERD model was established by esophagogastroduodenal anastomosis,the liver depression syndrome model was established by chronic unpredictable stimulation,and disease-syndrome combination model of GERD with the live-gastric disharmony syndrome was established by EGDA combined with CUS.Liver depression syndrome was evaluated by general manifestation,sucrose preference test and open field test,GERD model was evaluated by esophageal gross manifestation,esophageal epithelial HE pathology,Ghrelin in serum was detected by ELISA,the gastric tissue Ghrelin content was detected by IHC.Brain GHS-R1 expression by WB.Experiment2:66 SD rats were randomly divided into sham operation group(n=11),disease model group(n=11),and disease-syndrome combined model group(n=11),omeprazole group(n=11),Tongjiang granule low-dose group(n=11)and Tongjiang granule high-dose group(n=11).GERD model was established by esophagogastroduodenal anastomosis(EGDA),and disease-syndrome combination model of GERD with the live-gastric disharmony syndrome was established by EGDA combined with CUS.Omeprazole group,Tongjiang granule low dose group and Tongjiang granule high dose group were treated with drugs on the basis of disease combined model respectively.The model was made and the drug was administered for 4 weeks.The general condition of the animals was observed,sucrose preference test and open field test,GERD model was evaluated by esophageal gross manifestation,esophageal epithelial HE pathologyand.Brain GHS-R1 expression by WB.Results :Experiment1 : Compared with the blank group,the sucrose preference and the total number of grids in the open field experiment in the disease-syndrome combination model group were extremely significantly reduced(p<0.001),and the residence time in the central area was significantly reduced(P<0.01);compared with the blank group,The content of Ghrelin in the serum of rats in the disease-syndrome combination model group was significantly increased(P <0.001),and the expression of ghrelin positive cells in the gastric tissue and the expression of GHS-R1 protein in the hypothalamus were significantly different(P <0.001).Experiment2 : Tongjiang Granules can repair esophageal inflammatory damage.Compared with the model group combined with disease and syndrome,the sugar water preference of the high-dose Tongjiang Granules group was significantly increased(p<0.001);The number of grids and the residence time in the central area both increased(P <0.05).Compared with the combined disease and syndrome model group,Tongjiang granule high-dose histone protein expression decreased significantly,with significant statistical difference(p<0.01).Conclusion :Experiment1: EGDA combined with CUS can successfully prepare disease-syndrome combination model of GERD with the live-gastric disharmony syndrome.The expression of serum and stomach Ghrelin in disease-syndrome combination model group was significantly increased,and the expression of GHS-R1 protein in the hypothalamus was significantly increased.It shows that the Ghrelin/GHS-R1 pathway plays a role in the pathogenesis of GERD with the live-gastric disharmony syndrome.Experiment2 : Tongjiang granule can significantly improve esophageal inflammatory injury and depressive behavior in rats with gastroesophageal reflux disease.And down-regulate the expression of GHS-R1 protein in diseased rats and regulate the Ghrelin/GHS-R1 pathway,thereby improving the anxiety and depression associated with GERD. |
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