| Barrett esophagus(BE)is a metaplastic process in which the normalquamous epithelium of the distal esophagus is replaced by columnar linedepithelium and is the result of chronic gastroesophageal reflux,may beassociated with intestinal metaplasia or no intestinal metaplasia, accompaniedby special intestinal epithelial metaplasia is a precancerous lesion ofesophageal adenocarcinom(aEC),In recent years, the incidence of esophagealadenocarcinoma tends to be top in Western countries, but our country with thechanges in the structure of diet and the use of endoscopic techniques,theincidence and detection rates of barrett esophagues increased year by year. Butetiology and pathogenesis of BE remain unclear．Signaling pathways usually play a crucial role in diseases. Notch/Hes1and Wnt/β-catenin signaling pathwaies are important in the development ofBE,Foreign scholars have reported Wnt/β-catenin signaling pathway keygene Wnt2have an important role in the development of BE,And in the BEcell lines, Notch/Hes1signaling pathway and bile acid relationship have beenreported,but Wnt/β-catenin signaling pathway key gene Wnt1,β-catenin andNotch/Hes1signaling pathway in the rat model of BE has not been reported。Objective:This paper was to make an animal model of Barrett esophagus andinvestigate the expression levels of key genes such as Notch1, Delta, Hes1,Wntl and β-catenin in esophageal tissues to provide basis for Barrettesophagus treatment.Methods:1.Eighty8-week-old male Sprague-Dawley rats were randomized intofour groups, including control group, iron group, esophagogastroduodenalanastomosis(EGDA)group, esophagogastroduodenal anastomosis adding iorn (EGDA+Fe) group. Sham operation was operated in the fomrer two groupsand the last two groups underwent surgical operation to producegastroduodenoesophageal reflux. After2weeks, Iron Dextran were injectedintraperitoneum of the rats in EGDA+Fe group (30mg/kg, twice per week for30weeks). Five rats of each group were sacrificed at12week after operationand others at32week, and esophageal samples were taken. Their esophagieswere assessed for presence of inflammation, BE, and dysplasia by gross andmicroscopy observation.2.Expression of Notch1, Delta, Hes1, Wntl andβ-catenin were exmained innomal esophagus, esophagitis, and Barrett's esophagus byimmunohistochemical staining of S-P.Results:1. MortalityThe mortality of nomal group, iron group, EGDA group, EGDA+Fegroup were0%,0%,6.7%,10%, respectively, the mortalities of EGDA group,EGDA+Fe group compared with that in the nomal group and iron group weredifferent significantly(P<0.05). The mortalities between EGDA group andEGDA+Fe group were not different significantly(P>0.05).12weeks after surgery, the iron group, rough esophageal mucosaoccurred partly. Chronic inflammation and mild hyperplasia were observed inthe esophagus under the light microscope. There were more serious damage inesophageal mucosa in EGDA group and EGDA+Fe group: the disappearanceof pink mucosa, rough mucosa, scattered ulcers, hemorrhagic erosive lesionsand the most serious damage were band of white bark-like proliferativechanges.32weeks after surgery, the damage was more serious in groups but therewere no BE in iron group. BE in EGDA group, EGDA+Fe group were21.4%,49.1%, respectively. The incidence of BE were significantly different beweenEGDA group and EGDA+Fe group (P<0.05).2.Immunohistochemical staining1)The expression of Notch1and Delta in NE, RE, and BE were0.0428±0.0316,0.1636±0.0198,0.2368±0.0251, and0.0475±0.0208,0.1462±0.0304,0.2345±0.0376, respectively. The expression of them inBarrett esophagus was highest and significantly higher than the other twodiseases(P<0.05),2) The expression of Hes1and Wntl in NE, RE, and BEwere0.0691±0.0265,0.1599±0.0364,0.2473±0.0329,and0.0475±0.0208,0.1517±0.0281,0.2746±0.0440, respectively. The expression of them in Barrettesophagus was highest and significantly higher than the other twodiseases(P<0.05)3) The expression of β-catenin in NE, RE, and BE were0.0412±0.0334,0.1742±0.0184,0.2399±0.0304, respectively, This expressionin Barrett esophagus was highest and significantly higher than the other twodiseases(P<0.05).4) The correlation of relative expression among Notch1and Delta, Hes1were good (r=0.676,r=0.684), The correlation of relative expression amongwnt1and β-catenin was good (r=0.884), The correlation of relativeexpression among Notch1and β-catenin was good (r=0.630)Conclusions:1.Iron Dextran carl increase the injury of gastroduodenalesophageal reflux toesophageal mucosa andinduce the developement of BE．This model is safe andsuccessful．2.The key genes of Notch and Wnt signal pathways were significantlyincreased in BE, suggesting that those signaling pathways involved in thepathogenesis of Barrett's esophagus. |
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