Effect Of NF-κB And PPAR-γ On The Development Of Barrett's Esophagus And Esophageal Adenocarcinoma

1. Establishing a kind of new and safe animal model of BE and EAObjective: To establish a kind of new and safe animal model of BE and EA. Methods: 150 Sprague-Dawley rats were randomized into 4 groups, including control (nonreflux) group, iron(Fe) group, reflux group and reflux adding iron group. Esophagoduodenostomy was operated in the last two groups and sham operation in the former two groups. After 2 weeks, Iron Dextran were injected intraperitoneum of the rats in Fe group and reflux adding iron group (50mg/kg,twice per week for 18 weeks). 5 rats of each group were sacrificed at 8 week after operation and others at 20week, and esophageal samples were taken. All esophagi were assessed for presence of cancer, BE, and dysplasia by gross and microscopy observation. Results: At 8 week after operation, mucosal coarse was seen in Fe group by microscopy. There were severe injuries in esophagus of reflux group and reflux adding iron group. At 20 week, injuries were more severe. The incidence of BE , dysplasia and EA in reflux adding iron group were 38.9% , 22.2% and 11.1% and those in refulx group were 13.2%, 2.6% and0.0%. The incidence of BE in the reflux adding iron group was higher than that of the nonreflux group (P<0.05),but there was no significant difference in the incidences of dysplasia and EA between the two groups(P>0.05). While there were more samples with BE and dysplasia in the reflux plus iron group ,comparing to the those of reflux group and iron group, there was significant difference between them(P<0.05). Conclusions: Iron Dextran can increase the injury of gastroduodenalesophageal reflux to esophageal mucosa and induce the developement of BE and esophageal adenocarcinomain. This model is safe and successful.2. Association of NF-κB expression and the development of BE and EAObjective: To discover the role of NF-κB in the development of BE and EA.Methods: Animal model is the same as above. Esophageal samples were taken at 20 week. NF-κB epression were examined by immunohistochemical staining. Results: The protein expression level of NF-κB was few in normal esophageal squamous epithelium,but was more in BE and EA.There was a statistically significance in NF-κB staining(P < 0.01) among these three groups.Moreover, an increasing intendency was observed from normal esophageal squamous epithelium to BE and EA(rs =0.789 P <0.01). There was a statistically significance in NF-κB staining(P <0.01) among these four groups. Conclusions: The up-regulation of NF-κB may play an important role in the development of BE and EA.3. Association of PPAR-γexpression and the development of BE and EAObjective: To discover the role of PPAR-γin the development of BE and EA. Methods: Animal model is the same as above. Esophageal samples were taken at 20 week. PPAR-γepression were examined by immunohistochemical staining. Results: The level of PPAR-γprotein expression was low in normal esophageal squamous epithelium,in contrast to high expression in BE and EA(P<0.01).However,there was no a statistically significance in PPAR-γstaining(P > 0.05) between BE and EA.Moreover, The protein expression level of PPAR-γwas few in in nonreflux group and Fe group,but was more in reflux group and reflux adding iron group. There was a statistically significance in PPAR-γstaining(P<0.01) among these four groups.Conclusions: The change of PPAR-γprotein expression in BE and EA may be related to the development of BE and EA.