Correlation Analysis Between NERD And Anxiety And Depression In Patients With Poor PPI Response And The Therapeutic Mechanism Of Shugan Jiangni Hewei Prescriptio

Objective: The purpose of this study is to explore the influence of anxiety and depression psychological factors on the onset of NERD patients with poor PPI response,and to provide a preliminary clinical basis for traditional Chinese medicine to treat NERD from "stagnation".The central sensitization of NERD can be reversed by down-regulating the NGF/Trk A pathway,and the therapeutic targets of traditional Chinese medicine on central sensitization in NERD rats can be further clarified.Methods:Clinical research:A cross-sectional survey was conducted to collect NERD patients who visited the outpatient department and ward of Professor白光in The Affiliated Hospital of Liaoning University of Traditional Chinese Medicine from December 2020 to December 2021.According to their responses to PPI,they were divided into two groups,namely the poor PPI response group and the good PPI response group,and then conducted online questionnaire survey.The general situation,reflux symptoms,self-rating Anxiety Scale(SAS)score,self-rating depression Scale(SDS)score and TCM syndrome type were compared between the two groups.Experimental study:Forty-eight MALE SD rats were divided into 4 groups by random number table method,including blank group,NERD model group,Omeprazole group,Shugan Jiangni Hewei Decoction group,with 12 rats in each group.NERD rats were randomly induced by intraperitoneal injection of chicken ovalbumin(OVA)for basic sensitization combined with esophageal acid infusion and psychological stress intervention for two weeks.The model was evaluated by esophageal barrier changes such as esophageal epithelial space(DIS)and other indicators of rat behavior.Then the rats were treated with omeprazole enteric-coated tablet,Shugan Jiangni Hewei Decoction.The changes of DIS and synaptic vesicles in spinal dorsal horn of rats in each group were observed by electron microscopy,and the expressions of NGF/Trk A and C-FOS in spinal dorsal horn of rats in each group were detected by western blot and immunohistochemistry.RESULTS:1.A total of 138 patients were collected through the questionnaire survey,including 50 NERD patients with poor PPI response and 88 NERD patients with good PPI response.The average SAS score of the NERD group with poor PPI response was 50.22±7.791,which was significantly higher than the average SAS score of 43.11±10.519 in the NERD group with good PPI response(P<0.01).The average SDS score of the NERD group with poor PPI response was 50.22±7.791,which was significantly higher than that of the NERD group with good PPI response,40.91±9.255(P=0.001 < 0.01).In terms of gender,the proportion of women in the NERD group in the poor PPI response group was higher,with statistical significance(P=0.048<0.05),and the number of female patients with NERD with anxiety state was significantly more than that of men(P=0.034<0.05).There was no significant difference in the proportion of males and females in NERD with depression(P=0.073>0.05).The average disease duration of the NERD group with poor PPI response was 24.18±24.2207 months,which was significantly longer than that of the NERD group with good PPI response,which was 8.563±12.3779 months(P<0.01).In terms of the distribution of TCM syndrome types,in the NERD group with poor PPI response,21 cases(42%)of liver and stomach stagnation syndrome,8 cases(16%)of qi stagnation and phlegm block syndrome,8 cases(16%)of gallbladder heat invading stomach syndrome,There were 8 cases(16%)of middledeficiency and qi inverse syndrome,2 cases(4%)of spleen deficiency and damp-heat syndrome,and 3 cases(6%)of blood stasis syndrome.In the NERD group with good PPI response,41 cases(46.59%)of liver and stomach stagnation syndrome,10 cases(11.36%)of qi stagnation and phlegm block syndrome,10 cases(11.36%)of gallbladder heat invading stomach syndrome,and 13 cases of middle-deficiency qi reverse syndrome(14.78%),10cases(10.36%)of spleen deficiency and damp-heat syndrome,and 4 cases(4.55%)of blood stasis blocking collaterals.There was no significant difference in the distribution of syndrome types between the two groups(P=0.646>0.05).In the NERD group with poor PPI response,there was a correlation between the syndrome types and gender(χ2=20.574,P=0.001<0.05).Among them,the female NERD patients with Qi stagnation and phlegm obstruction syndrome were significantly more than men,and the male NERD patients with gallbladder heat attacking the stomach syndrome There were significantly more patients than women,and significantly more women than men had NERD.There was also a significant correlation between the syndrome types and gender in the NERD group with good response to PPI(χ2=11.531,P=0.042<0.05).Among them,there were significantly more male NERD patients than female NERD patients with liver and stomach stagnation heat and gallbladder heat attacking the stomach syndrome.There were significantly more female NERD patients than males.There was no significant difference between the two groups in terms of age,marital status,education level,and nature of work(P>0.05).2.In animal experiments,(1)Behavioral changes of rats in each group: in blank group,rats had good mental state,shiny and smooth hair,sensitive response,normal diet and water intake,and no abnormal defecation;Rats in NERD model group had listless mental state,withered hair,slow response,irritability,significantly reduced diet and water intake,and much mushy or watery stool volume.Mental state of the rats in omeprazole group was slightly weak,with dry hair,fair reaction,reduced diet and water intake,and sometimes unformed stool.The mental state of the rats in Shugan Jiangni and Weifang group was fair,the hair was still moist and smooth,the reaction was still sensitive,the amount of food and drink was slightly reduced,and the stool was occasionally not formed.(2)Esophageal mucosal epithelial space(DIS)of rats in each group was observed under electron microscopy: no erosion was observed in the esophageal mucosa of rats in the four groups.Compared with blank group,DIS in NERD group showed obvious irregular expansion;Compared with THE NERD group,DIS in the omeprazole group was slightly reduced,while DIS in the Shugan Jiangni and Weifang groups was significantly uniform.(3)The density of synaptic vesicles in spinal dorsal horn tissues of rats in each group was observed under electron microscopy: compared with blank group,the density of synaptic vesicles in spinal dorsal horn tissues of rats in NERD group was significantly increased.Compared with the NERD model group,the synaptic vesicle density of spinal dorsal horn of rats in the omeprazole group,shugan Jiangni group and Weifang group decreased,but the vesicle density of shugan Jiangni And Weifang group was lower than that of the Omeprazole group.(4)Western blot detection of NGF and Tr KA protein expressions in spinal dorsal horn of rats in each group: Compared with blank group,NGF and Tr KA protein expressions in spinal dorsal horn of rats in NERD group were significantly increased(P < 0.01);Compared with model group,NGF and Tr KA protein expressions in spinal dorsal horn of rats in Shugan Jiangni Heweifang group and omeprazole group were significantly decreased(P < 0.01),but NGF and Tr KA protein expressions in shugan Jiangni Heweifang group were significantly decreased compared with omeprazole group(P < 0.05).(5)Immunohistochemical detection of the expression of c-fos protein in the dorsal horn of the spinal cord of the rats in each group: a small number of c-fos positive neurons were found in the dorsal horn of the spinal cord of the rats in the blank group,and the coloration was light.A large number of c-fos positive neurons were seen in the dorsal horn of the spinal cord in the NERD model group,which were densely distributed and deeply stained.The positive distribution of c-fos in the dorsal horn of the spinal cord of rats in the omeprazole group was sparse and lightly stained.The dorsal horn of the spinal cord of the rats in the Shugan Jiangni and Weifang groups only had sporadic c-fos positive distribution,and the staining was lighter.On the H-Score,compared with the blank group,the expression of c-fos protein in the dorsal horn of the spinal cord of the rats in the NERD model group was significantly increased(P<0.001);The expression of c-fos protein in the spinal dorsal horn of the rats in the Weifang group and the omeprazole group was significantly decreased(P<0.001);Although the expression of c-fos protein decreased,there was no significant difference between the two(P=0.581>0.05).Conclusion:1.NERD patients with poor PPI response are more likely to develop anxiety and depression.In terms of the expression of NERD in traditional Chinese medicine,men are mostly anger depression and heat depression,while women are mostly qi depression and phlegm depression.2.Shugan Jiangni Hewei Decoction can significantly improve the mental state of NERD rats after stress,reduce the dilated esophageal DIS,reverse the expression of NGF/Trk A protein in the spinal dorsal horn tissue of rats to a certain extent,and reduce NERD Expression of c-fos protein and intersynaptic vesicle density in the dorsal horn of rat spinal cord after sensitization.