| Helicobacter pylori is the major cause of chronic gastritis and plays an important role in the pathogenesis of peptic ulcer and gastric adenocarcinoma. So far, however, the colonization and pathogenesis mechanisms of H. pylori remains unclear. H. pylori is highly adapted to the human stomach, and a high level of diversity is observed among clinical isolates. The polymorphism may be the consequence of adaptive changes during colonization and indicate that H. pylori hold specialized adaptability mechanism. Now that a strain passing from one human host to another undergoes adaptive changes leading to a high diversity of the clinical isolates, a strain passing from a human host to an animal host undergoes more important and consequently more easily detectable adaptive changes. Research on adaptive change of H. pylori during colonization in animals will be helpful to clarify the colonization and pathogenesis mechanisms of H. pylori. At present, however, most research associated with adaptive colonization has been focused on the genetic changes of related molecules or single or few proteins without systematic study. On the basis of these consideration, proteomic strategy, combined with two-dimensional electrophoresis (2-DE) separation and mass spectrometry(MS) identification with advantage of high resolution, high reproducibility was used to separate and identify differentially expressed proteins of H. pylori during adaptive colonization in Mongolian gerbils in this study. We hoped to find out a series of protein cluster involved in adaptive colonization and addressed the question whether there were new proteins to be associated with adaptive colonization, moreover, to clarify the colonization-associated function mediated by new candidate proteins.Main results are listed below:1. Establishment of Mongolian gerbil model infected with H. pylori and identification of the adaptive colonization strains Firstly, Clinical isolated strain M0 of H. pylori were inoculated into Mongolian gerbils. This strain that initially had grown only weakly in Mongolian gerbils was adapted during 13 serial passages in vivo. This resulted in an increase in infectious rate from about 2/10 to 9/10 , a adaptive colonization strain M13 has been abtained. Second, Mongolian gerbils were fed well-adapted strain M13 and observed during a 24 weeks period. The infectious rate and colonization density did not decrease 24 weeks after inoculation with M13 strain. Moreover, The gastritis and ulcer assimilated with human were observed in the infectious period. This results indicate a Mongolian gerbil model infected with H. pylori has been successfully established. The two strain M0 and M13 were observed by optic and electron microscope, M13 strain showed longer and more spiral. The two strain were analysed by SDS-PAGE and M13 strain showed a high-expressed 20KDa protein. All of these results suggest an adaptive variation of H. pylori occurring during colonization in Mongolian gerbils. 2. Study on the variation of proteome of H.pylori after adaptive colonization in Mongolian gerbilsTo search the proteome alternations associated with adaptive colonization of H. pylori, comparative proteomic technology was taken to separate and identify the global proteins significantly changed between H. pylori strain M0 and M13. Firstly, 12% SDS-PAGE following pH3-10L IPG strips in IEF was used to search differentially expressed proteins. The gels were scanned , and the images were processed with PDQuest software. The 2-D patterns were highly reproducible since each experiment was performed in triplicate and produced similar results. Average of 564±32 and 602±27 protein spots were detected in strain M0 and M13, respectively. The correlation coefficient between these two patterns are 0.78 by correlation analysis of gels. Then, 5 differential protein spots were cut out of gels for MALDI-TOF-MS identification. Database searching was performed using monoisotopic peptide masses obtained from MALDI-TOF-MS. Out of 5 spots excised from the gels, 4 spots were successf...
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