Establishment of Mongolian gerbil model of gastric cancer induced by Helicobacter pylori infection and its proteomics analysis
10.3760/cma.j.issn.0529-5807.2014.12.007
- VernacularTitle:幽门螺杆菌感染蒙古沙鼠胃癌模型的建立及蛋白质组学研究
- Author:
Yan ZHAO
1
;
Yuan XIE
;
Xian CHEN
;
Wenjie XU
;
Yan WANG
;
Jianjiang ZHOU
Author Information
1. 550004,贵阳医学院分子生物学重点实验室
- Keywords:
Helicobacter pylori;
Gerbillinae;
Stomach neoplasms;
Proteomics;
Disease models,animal
- From:
Chinese Journal of Pathology
2014;(12):820-826
- CountryChina
- Language:Chinese
-
Abstract:
Objective To establish an animal model of gastric cancer by long-term infection of Helicobacter pylori ( H.pylori ) and to elucidate the pathogenesis by proteomics analysis.Methods Fifty male Mongolian gerbils (4-5 week-old and weighted 60-100 g) were infected with H.pylori and the gastric tissues were obtained after the infection at 3, 6, 12 and 24 months.Histological changes were evaluated by H-E staining of the gastric tissue sections.Detection of H.pylori was performed by in-vitro culture of fresh gastric tissue samples, PCR amplification of H.pylori 16s rRNA and localization by silver staining.In addition, proteins extracted from gastric tissue samples were subjected to two-dimensional electrophoresis (2-DE) at various infection time points.Protein spots with increased quantity over the course of H.pylori infection were selected and analyzed by LC-MS/MS. Finally, differentially expressed proteins between human gastric cancer tissue samples and lymph nodes were analyzed by real-time RT-PCR.Results Colonization of H.pylori was observed in gastric tissue of gerbils as early as 3 months after H.pylori infection, and persisted till 24 months. Pathological examination of infected animals showed various histological changes including acute gastritis, atrophic gastritis, intestinal metaplasia and gastric carcinoma. Seventy-eight differentially expressed proteins were identified by proteomics analysis, among which 36 proteins were up-regulated and 42 were down-regulated. Analyzed by LC-MS/MS, ten proteins were identified, including lactate dehydrogenase, ATP synthase, fatty acid-binding protein, COX5B, peroxiredoxin-4, peroxide reductase, transgelin, succinyl-CoA ligase, keratin and protein disulfide- isomerase A2, among which transgelin, ATP synthase and lactate dehydrogenase were highly expressed in human gastric carcinoma and lymph nodes.Conclusions H.pylori infection induces the expression of transgelin, ATP synthase and lactate dehydrogenase, implying possible roles in the pathogenesis of gastric diseases including cancer.