The Research Of Epidemiology And Pathophysiological Echanisms In Pediatric Functional Dyspepsia

BackgroundWith the medical model conversion from single biological mode to thebiological-psychological-social mode, People show more and more solicitude forfunctional gastrointestinal disorders(FGIDs). Functional dyspepsia(FD) is a frequentkind of FGIDs, Rome III criteria FD must include one or more of followingsymptoms: bothersome postprandial fullness, early satiation, epigastric pain,epigastric burning with no evidence of structural disease, symptoms of FDsuggested to be of gastroduodenal origin. Rome III criteria proposed subdivision offunctional dyspepsia into epigastric pain syndrome and postprandial distresssyndrome.FD is a very common condition with a high prevalence throughout theworld, occurring in26%to34%of the general population. There is no systemicdomestic report about prevalence in Pediatric functional dyspepsia. To date, There isno definitive pathophysiologic mechanism for functional dyspepsia, which suggeststhat it is a heterogeneous group of disorders. For the past few years, the research ofpathophysiology focused on Hp infection, gastrointestinal hormone, and inflammatorycells.ObjectiveTo investigate the epidemiology of functional dyspepsia and the relation betweenfunctional dyspepsia and Hp infection among children in Suzhou. Explore the potentialrole of Ghrelin、leptin and PYY in functional dyspepsia. Research the correlationbetween FD and eosinophil quantity, Eotaxin and RANTES in gastric mucosa. Toprovide theory foundation for clinical prevention and therapeutics of Pediatric functional dyspepsia..Methods1Epidemiology study:A Cross-sectional survey12923pupil in Cang-lang district of Suzhou city,prescreening the children with epigastric pain or postprandial distress. Diagnosefunctional dyspepsia according to Rome III definition by questionnaire. Detect Hp by13C breath test.2Detect plasma ghrelin, leptin and PYY by ELISAOne hundred and twenty-four consecutive patients presenting with typicalsymptoms of FD (EPS, n=63; PDS, n=61) and twenty-seven healthy volunteerswere enrolled,Patients were diagnosed according to Rome III criteria, Helicobacter pyloriinfection was determined by the13C-urea breath test (HP+，n=62; HP-, n=62).Blood samples were obtained after an overnight fast of12h, immediatelytransferred to chilled polypropylene tubes containing Na2EDTA and aprotinin, thencentrifuged at4℃assemble plasma, immediately frozen in liquid nitrogen and stored at-70℃. Ghrelin, leptin and PYY were measured using commercially availableELISA kits according to the manufacturer’s instructions.3Determination of gastric mucosa ghrelin, leptin and PYY content by RT-PCR:Forty-three Consecutive patients with typical symptoms of FD undergoingroutine upper gastrointestinal endoscopy were enrolled, All samples were obtained withwritten informed consent of the patients prior to their inclusion, During endoscopy, twobiopsy specimens were obtained from the antrum, One specimen was used for rapidurease testing to detect the presence of H. pylori. Another specimen was immediatelyfrozen in liquid nitrogen and stored at-70℃for reverse transcriptase polymerasechain reaction (RT-PCR) and determination of tissue ghrelin, leptin and PYY l content.4Hematoxylin-eosin staining and ImmunohistochemistySeventy-one consecutive patients presenting with typical symptoms of FD andtwenty-one healthy volunteers were enrolled, During endoscopy, two biopsy specimenswere obtained from the antrum, One specimen was used for rapid urease testing to detect the presence of H. pylori. Another specimen was fixed for24hours in a3%formaldehyde solution and paraffin imbedded and sectioned at5mm. Sections werestained with hematoxylin-eosin-safran for histopathology examination.To select5clear and different high-power fields(×400),counting the number ofeosinophils. Immunohistochemisty staining was performed for observing theexpression of Eotaxin and RANTES.Results1Epidemiology results: Prevalence of FD is8%in12923pupil, prevalence of PDSis3%, prevalence of EPS is5%. Infection rate of Hp is27.3%in FD, There is nostatistical significance between PDS and EPS. Risk factors of PDS are: Young age,lower level of parents’ education, Saprodontia and Lower BMI; Risk factors of EPS are:Female, Saprodontia and BMI.2Plasma concentrations of ghrelin, leptin, PYY and H pylori status:Plasma ghrelin levels in FD is lower than in healthy volunteers, ghrelin in PDS islower than in EPS, ghrelin in Hp-positive is lower than in Hp-negative, difference wassignificant(P<0.001). Plasma leptin levels in FD is highe than in healthy volunteers,leptin in PDS is higher than in EPS, leptin in Hp-positive is higher than in Hp-negative,difference was significant(P<0.001). Plasma PYY levels in FD is higher than in healthyvolunteers, difference was significant(P<0.001). moreover, there was no significantdifference in PYY levels between EPS and PDS.3Detection of ghrelin，leptin and PYY mRNA:Using RT-PCR, ghrelin and leptin mRNA were identified in the gastric antrummucosa, but PYY mRNA was not detected.Gastric ghrelin contents in patients with Hp infection were significantly lower thanthose in uninfected subjects (P<0.001). In addition, Gastric leptin contents in patientswith Hp infection were significantly higher than those in uninfected subjects (P<0.001).4Eosinophils count and Immunohistochemisty results:In the gastric antrum mucosa, Eosinophils number and expression of Eotaxin andRANTES in Hp+and EPS/Hp-were significantly higher than those in PDS/Hp-andcontrol group (P<0.001). Chemotactic factor Eotaxin expression widespread in the intracytoplasm of mucosa and gland epithelial cells, RANTES expressionwidespread in the intracytoplasm and endonuclear of mucosa and glandepithelial cells and inflammation cells. Expression of Eotaxin and RANTES waspositive correlation with Eosinophils number in the gastric antrum mucosa.Conclusion1. Functional dyspepsia was a common pediatric disease in Suzhou, EPS was mainisoforms in pediatric functional dyspepsia. The risk factors of pediatric FD were: youngage, female, Saprodontia, lower education lever of parents’ and abnormal BMI.2. Ghrelin,leptin and PYY had an important potential role in pathogenesis offunctional dyspepsia, Ghrelin and leptin were specifically correlation with PDS. Ourstudy supported the potential of ghrelin mimetics as a novel approach to treat of PDS.3Eosinophils and chemotactic factors Eotaxin, RANTES were all associatedwith allergy and may indicate a hypersensitivity mechanism in some patients withEPS, And estabilished the new theorial and experimental foundation of the clinicalTherapeutics.