| Gastroesophageal reflux disease refers to a series of related symptoms caused by the reflux of gastroduodenal contents into the esophagus.Its typical symptoms are reflux and heartburn.Atypical symptoms are more common and easily ignored,including non-cardiogenic chest pain,chronic cough,foreign body sensation in the throat and hoarseness.Epidemiological survey shows that the incidence of gastroesophageal reflux disease in North America is as high as 27.8%,in Europe as high as 25.9%,and in Asia as high as 2%-7%.In recent years,the incidence of gastroesophageal reflux disease has further increased,especially in Asia,which has become one of the most common chronic diseases of the digestive system.The definition of gastroesophageal reflux disease was proposed at Genval(Belgium)International Conference in 1997.The endoscopic manifestations of gastroesophageal reflux disease include esophageal mucosal erosion,ulcer and other inflammatory lesions,which are called reflux esophagitis.But there are also quite a number of patients with gastroesophageal reflux disease who have no esophageal inflammatory changes under endoscopy,which are called endoscopic negative gastroesophageal reflux disease or non-erosive gastroesophageal reflux disease.Clinical studies show that the incidence of non-erosive gastroesophageal reflux disease is significantly higher than the other two subtypes of gastroesophageal reflux disease,accounting for about 70%of gastroesophageal reflux disease,which is the main type of gastroesophageal reflux disease.As a chronic disease caused by reflux of gastric contents,the acid suppression treatment led by proton pump inhibitors is still the main treatment method for non-erosive gastroesophageal reflux disease.However,proton pump inhibitors has poor response to intractable reflux and non-acid reflux,and there is a risk of complications caused by long-term use.Most patients can not tolerate proton pump inhibitors,resulting in recurrent symptoms,and even develop into refractory non-erosive gastroesophageal reflux disease.The characteristics of non-erosive gastroesophageal reflux disease,such as high incidence,easy recurrence,poor effect on proton pump inhibitors and difficult to cure,not only seriously affect the quality of life of patients,but also increase a great economic burden for patients and society.In traditional Chinese medicine,non-erosive gastroesophageal reflux disease attributable to"dysphagia","chest pain","spit acid","epigastric pain","despair an illusion of esophageal" and so on.The disease is located in the esophagus and stomach,which is closely related to liver,gallbladder,spleen and lung.Its basic pathogenesis can be summarized as liver and gallbladder failure to drain,stomach loss and descent,Stomach Qi upside down,and disease nature is deficient and marked.At present,the pathogenesis of non-erosive gastroesophageal reflux disease is not fully elucidated.Through our previous studies,we found that the Spleen deficiency and Qi reversed flow Type in non-erosive gastroesophageal reflux disease accounted for 19.09%,and the Spleen deficiency and Qi reversed flow Type in non-erosive gastroesophageal reflux disease recurrence patients was as high as 37.6%,indicating that the Spleen deficiency and Qi reversed flow Type in non-erosive gastroesophageal reflux disease is one of the more easily recurred types.At present,the pathogenesis of non-erosive gastroesophageal reflux disease is not fully elucidated.Esophageal hiatal hernia,dysfunction of lower esophageal sphincter,dysmotility of esophagus,impaired function of esophageal mucosal barrier,acid bag in stomach and psychosocial abnormalities are considered to be involved in the occurrence of non-erosive gastroesophageal reflux disease.Recent studies have shown that there is a special interstitial cell of ICC in the lower esophagus and gastrointestinal tract,immunohistochemical staining and electron microscopy showed that ICC was closely related to vasoactive intestinal peptide,nitric oxide,nitric oxide synthase and other neurotransmitters,vasoactive intestinal peptide,nitric oxide,nitric oxide synthase are important neurotransmitters in the gastrointestinal nervous system,involved in the transmission of neural signals,and then regulate and control smooth muscle.Further research found that ICC was in close contact with smooth muscle cells,especially circular muscle cells.When the neurotransmitter is transmitted to ICC,it generates excitatory or inhibitory electrical signals and then acts on smooth muscle cells to regulate the smooth muscle of esophagus and gastrointestinal tract.These new findings confirm that vasoactive intestinal peptide,nitric oxide,nitric oxide synthase and other neurotransmitters participate in and determine the tension,peristalsis and contraction of the esophagus,and the imbalance of these neurotransmitters is one of the important pathological mechanisms of non-erosive gastroesophageal reflux disease.The mechanism of vasoactive intestinal peptide,nitric oxide and nitric oxide synthase regulating esophageal sphincter and gastrointestinal smooth muscle and their relationship with ICC may become an important potential target for traditionalChinese medicine treatment of non-erosive gastroesophageal reflux disease.Therefore,to study the correlation between TCM syndromes of non-erosive gastroesophageal reflux disease and the expression of vasoactive intestinal peptide,nitric oxide and other neurotransmitters,as well as the intervention mechanism of TCM is a good entry point for the integration of TCM and Western medicine.However,up to now,the correlation between TCM syndromes of non-erosive gastroesophageal reflux disease and the expression of vasoactive intestinal peptide,nitric oxide and other neurotransmitters,as well as the regulation mechanism of TCM have not been reported systematically at home and abroad.So,In this experiment,we first studied the relationship between vasoactive intestinal peptide,nitric oxide,nitric oxide synthase and traditional Chinese medicine syndromes of non-erosive gastroesophageal reflux disease,so as to clarify the correlation between them,and then objectify the traditional Chinese medicine syndromes of non-erosive gastroesophageal reflux disease,and to provide objective basis for TCM dialectics of non-erosive gastroesophageal reflux disease.Moreover,this experiment tried to investigate the clinical efficacy of Liujunzi Decoction combined with Xuanfu Daizhe Decoction in the treatment of non-erosive gastroesophageal reflux disease with Spleen-Qi Deficiency Counterflow Type and its effect on the expression levels of plasma vasoactive intestinal peptide,nitric oxide and nitric oxide synthase,exploreing the regulatory mechanism of Chinese medicine intervention in non-erosive gastroesophageal reflux disease,and further revealing the new target of traditional Chinese medicine,and opening up new ideas for Chinese medicine to further overcome non-erosive gastroesophageal reflux disease.Part I Comparative analysis of clinical features of non-erosive gastroesophageal reflux disease and reflux esophagitisObjective:By comparing and analyzing the clinical features of NERD and RE,we can make clear the difference between them,and provide help for clinical prevention,diagnosis and treatment of GERD.Methods:146 patients diagnosed as NERD from May 2016 to August 2017 were selected,and 127 patients diagnosed as RE in the same period were selected as controls.The questionnaire of general demographic characteristics,RDQ score were filled out voluntarily,and gastroscopy and helicobacter pylori infection were performed voluntarily.Results:In general terms:(1)NERD is prevalent in women and mainly in the mental labor group.RE occurs in men and mainly in manual labor(P<0.05).NERD patients mainly live in rural areas,while reflux esophagitis patients mainly live in urban areas.(2)Lifestyle and predisposing factors:In NERD group,the proportion of BMI,obesity,smoking and alcohol consumption was lower than that of RE group(P<0.05),but the proportion of anxiety and depression was higher than that of RE group(P<0.05).(3)The course of disease and recurrence:Compared with RE group,the course of NERD group was longer,more likely to relapse,more recurrence times,and longer recurrence interval(P<0.05).(4)Clinical symptom characteristics:In NERD group,the heartburn,chest pain,belching and acid regurgitation,pharyngeal foreign body sensation of the incidence rate and severity is higher than that of RE group(P<0.05),the incidence of cough and severity is lower than RE group(P<0.05),and the incidence of chest tightness in NERD group was higher than that in RE group(P<0.05),but the severity was not statistically significant(P>0.05).(5)Overlap irritable bowel syndrome,functional dyspepsia:The incidence of overlap IBS and FD in NERD group was significantly higher than that in RE group(P<0.05).Conclusions:There is a marked difference between NERD and RE,and the results support the view that both are independent diseases rather than the different stages of the same disease.Therefore,the clinical treatment of NERD and RE should be treated differently.Part II Study on the correlation between TCM syndromes of NERDand the expression levels of VIP,NO and NOSObjective:To explore the correlation between TCM syndromes of NERD and the expression of vasoactive intestinal peptide,nitric oxide,nitric oxide synthase neurotransmitter index,so as to provide evidence for objectification of TCM syndromes of NERD.Methods:126 patients with NERD and 95 patients with RE in the control group were selected for TCM syndrome differentiation.The plasma levels of vasoactive intestinal peptide,nitric oxide and nitric oxide synthase were detected and the correlation between TCM syndrome and the three indicators was analyzedResults:The plasma levels of vasoactive intestinal peptide,nitric oxide and nitric oxide synthase in patients with NERD were significantly higher than those in patients with RE and healthy control group(P<0.05),and the most common TCM syndromes of NERD were liver-stomach stagnation-heat syndrome and spleen deficiency-dampness-heat syndrome;There were significant differences in plasma vasoactive intestinal peptide,nitric oxide and nitric oxide synthase neurotransmitter among different TCM syndromes of NERD;There was no significant correlation between plasma vasoactive intestinal peptide,nitric oxide,nitric oxide synthase and progression of NERD(P>0.05).Conclusion:Vasoactive intestinal peptide,nitric oxide and nitric oxide synthase may be involved in the occurrence and development of NERD.The differences in their expression levels are related to the TCM syndromes of NERD,which can provide objective basis for TCM syndrome differentiation and clinical diagnosis and treatment evaluation of NERD to a certain extent.Part ? Clinical efficacy of Liujunzi Decoction combined withXuanfu Daizhe Decoction in the treatment of NERD with Spleen deficiencyand Qi reversed flow Type and its effect on the expression levels of plasma VIP,NO and NOSObjective:To investigate the clinical efficacy of Liujunzi Decoction(LJZ)combined with Xuanfu Daizhe Decoction(XFDZ)in the treatment of NERD with Spleen-Qi Deficiency Counterflow Type and its effect on the expression levels of plasma VIP,NO and NOS.Methods:66 patients with NERD of Spleen-Qi Deficiency Counterflow Type were randomly divided into traditional Chinese medicine group(35 cases)and Western medicine group(31 cases).The Chinese medicine group was treated with LJZ and XFDZ,while the western medicine group was treated with rabeprazole combined with mosapride.Both groups were treated for 4 weeks.The symptom scores,total scores of the reflux disease questionnaire(RDQ)and the changes of TCM symptoms in the syndrome Spleen-Qi Deficiency Counterflow Type were compared before and after treatment in both groups.At the same time,the plasma levels of VIP,NO and NOS and nitric oxide synthase were monitored before and after treatment.Finally,the effective rate and late recurrence rate of the two groups were counted.Results:The scores of reflux,heartburn,non-cardiogenic chest pain,chest tightness,foreign body sensation in throat,belching,abdominal pain and total scores of RDQ in both groups were were significantly decreased after treatment(P<0.05),and the scores of reflux,heartburn,chest tightness,belching and total scores of RDQ in the traditional Chinese medicine group were significantly lower than those in the western medicine group(P<0.05);The number of cases of vomiting clear water,belching,eating less and taking dull meals,fatigue,gastric fullness and thin stool in the Chinese herbal medicine group decreased significantly after treatment(P<0.05),and the number of cases of vomiting clear water and belching in western medicine group decreased significantly after treatment;The levels of VIP and NO in plasma decreased after treatment in both groups,and the levels of VIP and NO in plasma of TCM group were significantly lower than those of Western medicine group(P<0.05),while the levels of NOS in plasma of TCM group decreased after treatment(P<0.05).In addition,plasma NOS decreased in Chinese medicine group(P<0.05),but increased in western medicine group(P>0.05);The total effective rate of the Chinese medicine group was higher than that of the western medicine group,and the recurrence rate was significantly lower than that of the western medicine group(P<0.05).Conclusion:LJZD combined with XFDZD can effectively improve the symptoms of NERD,reduce the recurrence rate,and significantly reduce the expression levels of plasma VIP,NO and NOS in patients with NERD.It can be inferred that VIP,NO and NOS neurotransmitters are important potential targets for traditional Chinese medicine in the treatment of NERD. |
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