| Background:Gastric mucosa has defense mechanisms to prevent injury by a variety of physical and chemical substances, including mucus-bicarbonate barrier, mucosal barrier, mucosal blood flow and epithelial cell renewal. Gastric mucosal barrier consists of epithelial cells and connections between components, which can effectively prevent the diffusion of H+reverse and macromolecules invasion, and served as the first line of defense to prevent harmful microorganisms invade the body through the stomach. Connections between cells make up by tight junctions, adhesion connection, gap junctions and desmosomes and other components. Once tight junctions were damaged, bacteria and endotoxin can enter the body through the tight junctions with increased permeability between epithelial cells which are related to the development of many diseases. Helicobacter pylori (Hp) infection is regarded as main pathogenetic factor of chronic gastritis, peptic ulcer, gastric adenocarcinoma, and mucosa-associated lymphoid tissue lymphoma, but its pathogenesis is unclear. Children are susceptible group of Hp infection which is also related with chronic gastritis, duodenitis, and peptic ulcer development. Epidemiological data showed that more than50%Hp-infected patients were infected with Hp starting in childhood. Gastric epithelial barrier function damage plays an important role in the pathogenesis of Hp-related gastric diseases. However, the effect of Hp infection on the gastric epithelial barrier function in children is still unclear. It was very important to study the tight junction protein expression of gastric mucosa and its changes in children with Hp infection for understanding the pathogenesis of Hp associated gastric disease.Objective:To understand the junction protein expression of gastric mucosa including occlusal proteins (occludin), closed protein (claudin), zonula occludens (ZO-1), epithelial cadherin (E-cadherin), and β ring protein (β-catenin) and the clinical significance in children with Hp infection.Methods:The patients performed by gastric endoscopy because of nausea, vomiting, abdominal pain, bloating, acid reflux, melena, and other gastrointestinal symptoms were enrolled in this study from May to Novemeber in2011in Children’s Hospital affiliated Zhejiang University School of Medicine. Informed consent was signed by their parents, and the study was in accordance with the principles of medical ethics. Three gastric antrum specimens were biopsied; one for rapid urease test (RUT), one for a fixed in10%formalin submission pathology, and the last one was preserved at-80℃after cryopreservation in liquid nitrogen refrigerator. The mRNA levels and protein expression of tight junction protein of gastric mucosa was measured by RT-PCR and western blot respectively. The location and semi quantitative of E-cadherin and β-catenin in gastric mucosa were detected by immunohistochemistry staining method.Results:Fourty one cases aged3.5-16years old (male28cases, female13cases) had complete clinical and pathological data were analyzed in this study. Of them,27cases were Hp positive and14cases were Hp negative according to the result of RUT and gastric mucosa pathology detection. In the Hp positive group,13cases were diagnosed with peptic ulcer, and14cases without peptic ulcer. The mRNA level of ZO-1, E-cadherin, P-catenin in the Hp positive group regardless of peptic ulcer was significantly lower than that in the Hp negative group (all P<0.01).The expression of claudin-4in Hp positive gastric ulcer group increased obviously, the difference was statistically significant (P<0.01), while the difference of occludin levels was no statistical significance among the three groups. Immunohistochemistry results showed that E-cadherin, β-catenin levels in the Hp positive patients were also significantly lower than that in the Hp negative group (P<0.01and<0.05, respectively).Conclusion:Our results revealed that the tight junction protein ZO-1, E-cadherin, β-catenin expression of gastric mucosa were decreased in children with Hp infection, while claudin-4expression was increased in patients with peptic ulcer, suggesting that gastric epithelial barrier function damage may be the main pathogenesis of Hp associated gastric diseases in children. |
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