The Diversity Of Ghrelin In Gastric Mucosa And Plasma From Cases With Reflux Esophagitis

Objective: The epidemiologic studies have shown that an increasing incidence in gastroesophageal reflux has followed with the falling infection rate of helicobacter pylori (H.pylori) in developed countries. Some researches discovered that Ghrelin in plasma increases significantly after H.pylori eradication. Ghrelin can lead to appetite increasing and weight gain, which maybe one of reasons that the population of obesity is increasing in western countries paralleling by the falling tendency on H.pylori infectious rate. Recent studies have indicated that obesity can induce the occurrence of gastroesophageal reflux. But the experiments in human showed that Ghrelin level is lower in the obesitas people than that with normal BMI. GERD is a common disease with upper gastrointestinal dyskinesia. Reflux esophagitis (RE) is one type of GERD.As all known, transient lower esophageal sphincter relaxations(TLESR) is considered as the capital mechanism of GERD.Delayed gastric emptying may also contribute to GERD.The postulated mechanism is that intragastric pressure increasing is apt to defeat LES and leads to esophageal reflux. Ghrelin is a 28-amino acid polypeptide that has been identified as an endogenic ligand for growth hormone secretagogue receptor.Ghrelin influences appetite and energy balance.It is primarily produced by Gr neuroendocrine cells in gastric oxyntic gland area, which is the main source of circulating Ghrelin.Studies have revealed that Ghrelin has obvious effect on enhancing gastrointestinal motility.It was shown that Ghrelin accelerates gastric emptying,enhances small bowel transit and overcome postoperative ileus.In addition, lots of studies have showed that Ghrelin induces migrating myoelectric complexes(MMC) at interdigestive phase via vagal nerves. Acting on proximal stomach suggests that Ghrelin may prevent reflux by increasing LES pressure. At present, there are few reports about the relation of Ghrelin and reflux esophagitis.This experiment reseaches the diversity of Ghrelin in gastric mucosa and plasma from cases with RE in order to make clear of function of Ghrelin in reflux esophagitis, so as to offer experimental basis to pathogenesy of GERD.Methods: The study objects: case group includes 32 cases with reflux esophagitis (20male/12female), whose mean age is 45.2 year-old with 25.2 kg/m2 of mean body mass index(BMI) ; Control group contains 15 objects (male 9/ female 6), whose mean age is 44.9 year-old ,and mean body mass index 25.1 kg/m2, which have no gastroesophageal reflux symptoms and esophageal mucosa lesion under endoscopy. Two groups have no obvious deviation in gender, age and BMI. The study exclusion criteria involve the patients with hypertension, coronary artery disease, diabetes mellitus, cirrhosis of liver, renal disfunction, cerebrovascular disease, tumor, peptic ulcer, pyloric obstruction, as well as using glucocorticoid, non- steroidal anti-inflammatory drug and alcohol abuse recently. H.pylori test results are negative in both groups. The selected cases accept endoscopy to observe esophageal mucosa and take biopsy. The extent of esophageal lesion is assessed in accordance with the Los Angeles (LA) classification during endoscopy examination. A piece of gastric mucosa taking from antrum is used for H.pylori rapid urease test. 2 pieces of mucosal tissue are taken from gastric fundus, which is imbedded with paraffin, cut into slices and used to detect the expression of Ghrelin by immunohistochemical staining. 2 fasting blood samples are obtained in same day, one for determing plasma Ghrelin by radioimmunoassay (RIA) and another for serum H.pylori antibody. The result of immunohistochemical staining is analyzed with semi-quantitative pathological immage analysis system.The experimental measurement data is demonstraed in mean±standard deviation.The analysis of variance(ANOVA) is adopted in the group comparison and the data is measured by statistic software SPSS 12.0.Results: 32 cases in case group are found as 10 at grade A, 15 at grade B and 7 at grade C under endoscopy according to LA classification standard. Immunohistochemical staining showed that Grhelin positive cells are mainly expressed at the neck and bottom of gastric oxyntic glands in both groups.The expression of Ghrelin is significantly decreased in case group compared with control(393.52±49.29 vs 430.93±47.53,P<0.05). Furthermore,Ghrelin expression become weaker in according with LA classification:grade A(412.86±48.42),B (388.89±45.56) and C(375.81±56.11);Ghrelin level in grade B or C is signific- antly decreasing compared with controls (P<0.05).Plasma concentration of Ghrelin is significant decreasing in case group compared with controls (1.48±0.98ng/ml vs 2.16±1.23ng/ml,P< 0.05).According with LA classification,the plasma level of Ghrelin became weaker too:grade A (1.91±0.95ng/ml),grade B(1.39±1.09ng/ml),and C(1.07±0.74ng/ml),Ghrelin plasma lev- el in LA B or C is significantly decreased compared with controls (P<0.05).Conclusions: The expression of Ghrelin in cases with RE is significantly lower than that of controls. Change of Ghrelin level in plasma is according with it in gastic mucosa, which confirms circulating Ghrelin is mainly produced from gastric mucosa. Ghrelin has distinct gastroprokinetic effect and can accelerate gastric emptying. Decreased Ghrelin level maybe delay gastric emptying and lead to elevating of the intragastric pressure, which can increase the frequency of transient lower esophageal sphincter relaxation. So Ghrelin may play a role in genesis of reflux esophagitis. In addition, Ghrelin level changes along with the severity of reflux esophagitis correspondingly, which shows that Ghrelin may play a role in progression of reflux esophagitis.The result may offer an experimental basis for the pathogenesy of GERD.