Clinical Study On Biology Basis Of Metabolic Group "chronic Atrophic Gastritis Spleen - Stomach Damp - Heat Syndrome"

Objective:Chronic atrophic gastritis (CAG) is a histopathological manifestation of gastric mucosa under electronic endoscopy, which have longer duration and may be cancerization. The pathogenesis of CAG hasn’t been unified and no effective eradication therapy or interventions have been found. There is no specific clinical manifestations of CAG, and generally performances by upper abdominal fullness, loss of appetite, dull pain in epigastrium, weight loss and etc. These can be the gastric precancerous manifestations and intestinal type of gastric cancer could be developed from CAG. Therefore, CAG is always recognized as the most difficult digestive disease to treat. Many patients refuse to take the examination because the manifestation is faint and the patients couldn’t suffer the invasion of gastrointestinal endoscopes. Thus, it’s hard to achieve "early diagnosis and early treatment" of CAG. In TCM, there are many unique treatments with splendid effects to CAG, which could help some patients improve their precancerous conditions. The development of CAG treatment is limited by the losses of the standards and material basis of its syndrome differentiation and treatment of Spleen-Stomach-Dampness-Heat pattern standard based on TCM theory, and there is no objective and quantitative laboratory index to achieve the standardization and scientization of individual therapy. This study reveals the pathological state, biomarkers, potential pathogenesis and the material basis of Spleen-Stomach-Dampness-Heat pattern of CAG, by using 1H-NMR, LC-MS, GC-MS to qualitative or quantitative detect the blood and urine metabolite of CAG patients, especially the Spleen-Stomach-Dampness-Heat pattern. The results of this study would provide a new idea to study the CAG based on the TCM syndrome differentiation and treatments.This thesis is divided into two parts:The first part is the integrated Chinese and Western medicine literature review, which summarizes the progress of metabolomics used in Spleen-Stomach-Dampness-Heat pattern. The first chapter summarizes the development of CAG Spleen-Stomach-Dampness-Heat pattern research; the second chapter introduces the development and advantages of metabolomics to study the disease and patterns. The second part is experimental results of CAG and Spleen-Stomach-Dampness-Heat pattern based on metabolomics. There are the results and discussion, in this part the results reveal the pathological states of CAG Spleen-Stomach-Dampness-Heat pattern, try to find biomarkers, and find the potential pathogenesis and material basis of this pattern.Methods:(1) We collected blood and urine of 65 CAG subjects and 40 subjects as normal control group, using 1H-NMR metabonomics technology obtained metabolic spectra,after the normalization of the integral values obtained import software principal component analysis (PCA) to give the principal component (PC), re-use PC for each set of samples metabolic spectra partial least squares-discriminant analysis (PLS-DA) and orthogonal partial least squares-discriminant analysis France (OPLS-DA), draw the corresponding picture, so as to visually display each set of samples metabolites group information and identify characteristic differences metabolites. (2) In 65 patients, we choose 28 subjects in Spleen-Stomach-Dampness-Heat as the experimental group,17 cases of CAG Stomach Deficiency Syndrome as the control group, using the same analytical methods described above metabolomic analysis of two sets of plasma, to identify all the differences between two substances trends in the group.Results:(1) 65 patients in this study, female 43 cases,22 males and 30 years minimum age, maximum age 70 years, mean age was 52.54±9.54 years; diagnosed with intestinal metaplasia in 58 cases,89.23% of the total number of cases. (2)The results of this experiment found that:compared with the healthy control group, CAG plasma glucose, alanine, valine levels increased; glutamic acid, glycine, lactic acid, betaine, mannitol and other differences in metabolite levels were reduced, the difference was statistically significant (P<0.05). Urine xanthine, hippuric acid, citric acid content increased, creatinine, histidine, creatine, ornithine, creatine phosphate and other differences between Generations content were lower, the difference was statistically significant (P<0.05).(3) Plasma Metabolic Research Group for Traditional Chinese Medicine Spleen found:valine, lactulose compared spleen Deficiency Syndrome levels were lower, the difference was statistically significant (P<0.05); isobutyric acid, formic acid, carnosine relatively empty stomach content were higher in patients with cold syndrome, the difference was statistically significant (P<0.05).Conclusion:(1) Chronic atrophic gastritis patients mean age was 52.54±9.54 years, which is China CAG patients with an average age at diagnosis was little difference in the elderly. Wherein the more the number of 51 to 60 year-old patient, consistent with the existing epidemiological findings.(2) Glucose, alanine, valine, glutamic acid, glycine, lactic acid, betaine, xanthine, hippuric acid, citric acid, creatinine, histidine, creatine, ornithine, creatine phosphate and other substances involved in the the development of CAG, CAG may be used as molecular markers for early diagnosis. CAG further explanation of the development of energy metabolism, mass transfer, signal transduction pathways and gastrointestinal flora metabolism and biochemical pathways disorders. (3) Metabolite valine, lactulose, isobutyric acid, formic acid, carnosine may be the difference between CAG Spleen-Stomach-Dampness-Heat potential markers.