Effect of dietary anti-urease immunoglobulin Y on Helicobacter pylori infection in Mongolian gerbils

BACKGROUND AND AIM: Helicobacter pylori is known to be a major pathogenic factor in the development of gastritis, peptic ulcer disease and gastric cancer. Recently, chicken egg yolk immunoglobulin Y (IgY) has been recognized as an inexpensive antibody source for passive immunization against gastrointestinal infections. The present study was designed to investigate the effect of anti-urease IgY on H. pylori infection in Mongolian gerbils. METHODS: H. pylori-infected Mongolian gerbils were administered a diet containing anti-urease IgY, with or without famotidine (F). After 10 weeks, bacterial culture and measurement of the gastric mucosal myeloperoxidase (MPO) activity were performed. In a second experiment, another group of gerbils was started on a diet containing F + IgY a week prior to H. pylori inoculation. After 9 weeks, these animals were examined. RESULTS: In the H. pylori-infected gerbils, there were no significant differences in the level of H. pylori colonization among the different dietary and control groups. However, the MPO activity was significantly decreased in the H. pylori group administered the F + IgY diet compared with that in the H. pylori group administered the IgY, F, or control diet. Furthermore, in the gerbils administered the F + IgY diet prior to the bacterial inoculation, inhibition of H. pylori colonization and suppression of the elevated gastric mucosal MPO activity were observed. CONCLUSIONS: Oral administration of urease-specific IgY not only inhibited H. pylori disease activity in H. pylori-infected gerbils, but also prevented H. pylori colonization in those not yet infected. These encouraging results may pave the way for a novel therapeutic and prophylactic approach in the management of H. pylori-associated gastroduodenal disease.     

Influence of vitamin E on gastric mucosal injury induced by Helicobacter pylori infection

We investigated the effect of vitamin E on gastric mucosal injury induced by Helicobacter pylori (H. pylori) infection. Male Mongolian gerbils were divided into 4 groups (normal group without H. pylori infection, vitamin E-deficient, -sufficient and -supplemented groups with H. pylori infection). Following oral inoculation with H. pylori (ATCC43504 2 x 10(8) CFU), animals were fed diets alpha-tocopherol 2 mg/100 g diet in the normal and vitamin E-sufficient groups and alpha-tocopherol 0.1 mg/100 g and 50 mg/100 g in the vitamin E-deficient and -supplemented groups, respectively, for 24 weeks. Chronic gastritis was detected in all gerbils inoculated H. pylori. Gastric ulcer was detected in 2 of 7 gerbils only in the vitamin E-deficient group. In the vitamin E-deficient group, myeloperoxidase activity and mouse keratinocyte derived chemokine (KC) in gastric mucosa was significantly higher than in the vitamin E supplemented group. Subsequently, in an in vitro study expression of CD11b/CD18 on neutrophils was enhanced by H. pylori water extract. This effect was suppressed in a dose dependent manner by the addition of alpha-tocopherol. These results suggest that vitamin E has a protective effect on gastric mucosal injury induced by H. pylori infection in gerbils, through the inhibition of accumulation of activated neutrophils.     

Effects of dexamethasone and FK506 on Helicobacter pylori-induced gastritis and bacterial viability in Mongolian gerbils.

FK506 and dexamethasone were used to investigate whether or not immunosuppression affects H. pylori colonization and gastric mucosal damage induced by Helicobacter pylori in Mongolian gerbils. Two weeks after H. pylori infection, FK506 and dexamethasone or vehicle alone were subcutaneously administered once daily for the following 2 weeks. FK506 or vehicle alone was administered subcutaneously once daily for 5 weeks (1 week before and 4 weeks after infection). In H. pylori-infected animals for 4 weeks, hemorrhagic erosions and inflammatory responses (neutrophil infiltration and lymphoid follicle formation) were induced in gastric mucosa at an incidence of 100%. Both FK506 and dexamethasone administered for 2 weeks markedly reduced such mucosal changes. In these animals, H. pylori viability in the stomach was significantly elevated. FK506 administered for 5 weeks also significantly inhibited the hemorrhagic erosions, edema and neutrophil infiltration in the stomach. H. pylori viability was slightly elevated as compared with the control. It was concluded that the host immune responses might play dual roles both by deteriorating gastritis induced by H. pylori and by protecting against H. pylori infection in its early stage.     

Gastric mucosal changes induced by long term infection with Helicobacter pylori in Mongolian gerbils: effects of bacteria eradication.

Helicobacter pylori infection has been reported to induce various mucosal changes, including gastric adenocarcinoma, in Mongolian gerbils 62 weeks after inoculation. Using Mongolian gerbils, this study examined whether or not eradication of the bacteria with drugs at specified times after infection prevents the development of mucosal changes. After orally inoculating with H. pylori (TN2GF4, vacA- and cagA-positive), the animals were killed 18 months later. Four or 8 months after H. pylori inoculation, eradication was performed by concurrent treatment with omeprazole+clarithromycin. Immediately after treatment ended, in both the 5 and 9 month groups, it was verified that H. pylori was completely eradicated. Autopsy performed 18 months after H. pylori inoculation revealed gastric hyperplastic polyps with erosive lesions and ulcers that were grossly visible in the non-treated control group. In addition, atrophic gastritis, intestinal metaplasia, carcinoids, and adenocarcinomas were histologically observed in the animals. In animals eradicated after 4 months and autopsied after 18 months, however, such mucosal changes were not observed. In contrast, intestinal metaplasia and mucosal atrophy was observed in animals eradicated after 8 months and autopsied after 18 months. It was concluded that early eradication of H. pylori infection with drug therapy can prevent severe gastric mucosal changes, to include adenocarcinomas, in Mongolian gerbils.     

Role of cyclooxygenase-2 in Helicobacter pylori- induced gastritis in Mongolian gerbils

Cyclooxygenase (COX)-2 expression is induced in the gastric mucosa of Helicobacter pylori-infected patients, but its role remains unclear. We examined the effects of NS-398 and indomethacin on gastric pathology in H. pylori-infected Mongolian gerbils. COX-1 was detected in both normal and H. pylori-infected mucosa, whereas COX-2 was expressed only in the infected mucosa. PGE(2) production was elevated by H. pylori infection, and the increased production was reduced by NS-398, which did not affect PGE(2) production in normal mucosa. Indomethacin inhibited PGE(2) production in both normal and infected mucosa. Hemorrhagic erosions, neutrophil infiltration, lymphoid follicles, and epithelium damage were induced by H. pylori infection. NS-398 and indomethacin aggravated these pathological changes but did not increase viable H. pylori number. H. pylori-increased production of neutrophil chemokine and interferon-gamma was potentiated by NS-398 and indomethacin. Neither NS-398 nor indomethacin caused any pathological changes or cytokine production in normal animals. These results indicate that COX-2 as well as COX-1 might play anti-inflammatory roles in H. pylori-induced gastritis.     

Long-standing gastric mucosal barrier dysfunction in Helicobacter pylori-induced gastritis in mongolian gerbils

BACKGROUND AND AIMS: Helicobacter pylori infection causes chronic gastritis and leads to peptic ulcer and gastric adenocarcinoma. An impaired gastric mucosal barrier could be involved in these processes. Our aim was to investigate gastric barrier function in H. pylori-induced gastritis. METHODS: Stripped gastric mucosal tissues of H. pylori-infected Mongolian gerbils (4 weeks and 70 weeks after inoculation, respectively) and controls were mounted in Ussing chambers. (51)Cr-EDTA (paracellular probe) and horseradish peroxidase (HRP, protein antigen) were used to assess mucosal barrier function. The electrophysiological parameters of the mucosa (transepithelial potential, short circuit current, and transepithelial resistance) were monitored as measurements of barrier integrity and viability. Tissue histology was performed to assess inflammation. RESULTS: In the antrum, both short-term gastritis [4.68 (3.88-5.74) x 10(-6) vs. control 2.86 (2.34-3.77) x 10(-6) cm/s, p <.001] and gastritis of long-standing [5.72 (3.88-10.94) x 10(-6) cm/s, p <.001 vs. control] showed increased permeability to (51)Cr-EDTA. In long-standing antral gastritis there was also an increased HRP flux [9.01 (2.98-45.02) vs. control 0.52 (0.06-1.20) pmol/h/cm(2), p <.001]. In the corpus, permeability to (51)Cr-EDTA was increased only in long-standing gastritis [4.63 (3.64-7.45) x 10(-6) vs. control 2.86 (2.12-3.98) x 10(-6) cm/s, p <.01]. Gastric mucosal permeability to (51)Cr-EDTA was correlated to histological inflammation and inflammatory activity. The levels of serum anti-H. pylori immunoglobulin G were positively correlated to HRP flux and (51)Cr-EDTA permeation. CONCLUSIONS: Helicobacter pylori-induced gastritis in Mongolian gerbils was associated with a long-standing gastric mucosal barrier dysfunction. The barrier defect extended from the antrum into the corpus over time. This impaired barrier function may contribute to perpetuation of chronic inflammation and may be involved in H. pylori-associated carcinogenesis.     

Helicobacter pylori-associated gastric pro- and antioxidant formation in Mongolian gerbils

Helicobacter pylori colonized gastric mucosa is manifest in a significant neutrophil infiltration with an extensive level of oxyradical formation. Mongolian gerbil is one of the excellent models for H. pylori-infection. The present study was designed to investigate pro- and antioxidant formation in the stomach of H. pylori-positive gerbils. Fourteen male Mongolian gerbils (MGS/Sea) were orally inoculated with H. pylori (ATCC43504) (Hp group) and 15 gerbils were inoculated with the culture media (Control). H. pylori infection was confirmed by the serum anti-H. pylori IgG test. Each gerbil was evaluated 6 or 12 weeks after the inoculation. Neutrophil infiltration was assessed by the tissue MPO activity. Mucosal oxidative stress was evaluated by thiobarbituric acid-reactive substances (TBARS), total glutathione contents, glutathione peroxidase (GSHPx) activity and Cu-, Zn-superoxide dismutase (SOD) activity. In Hp group, the H. pylori was persistently infected until 12 weeks. The level of MPO activity was significantly higher in Hp group at 6 and 12 weeks. Although the levels of TBARS and total glutathione were within the same range as controls at 6 weeks, they were significantly increased at 12 weeks. However, GSHPx activity was significantly increased at 6 weeks, but became the same range with the controls at 12 weeks. SOD activity showed no significant increase in Hp group at 6 and 12 weeks. In conclusion, H. pylori inoculation induced gastric mucosal neutrophil activation and pro-oxidant formation and also increased total glutathione contents, one of the mucosal antioxidants in gerbils.     

Role of bacterial strain diversity of Helicobacter pylori in gastric carcinogenesis induced by N-methyl-N-nitrosourea in Mongolian gerbils

AIM: Helicobacter pylori is known to enhance gastric carcinogenesis induced by chemical carcinogens. We previously demonstrated that infection with H. pylori strain SS1 did not enhance such carcinogenesis in C57BL/6 mice. Whether this result was due to the bacterial strain SS1 or to the experimental host, C57BL/6 mice, should be addressed. Therefore, we examined whether H. pylori strains introduced to the same host (Mongolian gerbils) differed in carcinogenicity. MATERIALS AND METHODS: H. pylori TN2GF4 strain (CagA(+), VacA(+)) and SS1 strain (CagA functionally(-), VacA(-)) were infected to Mongolian gerbils (n = 126). In the first experiment (induction of gastritis), histologic change in gastric mucosa of gerbils infected by H. pylori (TN2GF4, SS1, vehicle) without N-methyl-N-nitrosourea (MNU) at 1 month or 6 months was assessed. In the second experiment (experimental carcinogenesis), H. pylori (TN2GF4, SS1, vehicle) was inoculated to the gerbils after administration of MNU for 10 weeks, and the number of cancers and histopathologic changes at week 54 were assessed. RESULTS: In the first experiment, activity and inflammation in the TN2GF4 group were significantly greater than in the SS1 group at 1 month, while no significant difference was noted at 6 months. On the other hand, intestinal metaplasia and atrophy were significantly greater with TN2GF4 than with SS1 at 6 months but not at 1 month. In studies on experimental carcinogenesis, microscopically, 47.8% (11/23), 26% (7/26), and 0% (0/26), of animals had gastric adenocarcinoma in the MNU + TN2GF4 group, MNU + SS1 group, and MNU alone group, respectively. CONCLUSION: Both H. pylori strains, TN2GF4 and SS1, promoted carcinogenesis in Mongolian gerbils. The severity of gastritis and destruction and restoration of gastric mucosa may be related to gastric carcinogenesis. That the SS1 strain significantly accelerated carcinogenesis only in Mongolian gerbils and not in C57BL/6 mice suggests the crucial role of host factors in carcinogenesis by H. pylori infection.     

Effect of probiotics and triple eradication therapy on the cyclooxygenase (COX)-2 expression, apoptosis, and functional gastric mucosal impairment in Helicobacter pylori-infected Mongolian gerbils

BACKGROUND: Helicobacter pylori infection in Mongolian gerbils is an established experimental model of gastric carcinogenesis that mimics H. pylori-positive patients developing gastric ulcer and gastric cancer, but the effect of probiotic therapy on functional aspects of this infection remains unknown. METHODS: We compared the effects of intragastric inoculation of gerbils with H. pylori strain (cagA+ vacA+, 5 x 10(6) colony forming units/ml) with or without triple therapy including omeprazole, amoxicillin, and tinidazol or probiotic bacteria Lacidofil. Histology of glandular mucosa, the viable H. pylori, and density of H. pylori colonization were evaluated. The gastric blood flow was measured by H2-gas clearance method; the plasma gastrin and gastric luminal somatostatin were determined by RIA and expression of cyclooxygenase (COX)-2 and apoptotic Bax and Bcl-2 proteins were evaluated by Western blot. RESULTS: The gastric H. pylori infection was detected in all animals by histology and H. pylori culture. Basal gastric acid was significantly reduced in H. pylori-infected animals but not in those with triple therapy or Lacidofil. Early lesions were seen already 4 weeks upon H. pylori inoculation and consisted of chronic gastritis and glandular atypia associated with typical regenerative hyperplasia and increased mitotic activity and formation of apoptotic bodies. The H. pylori infection was accompanied by the fall in gastric blood flow, the marked increase in plasma gastrin, the significant fall in gastric somatostatin levels and Bcl-2 protein expression, and the rise in expression of COX-2 and Bax proteins. These mucosal changes were counteracted by the triple therapy and Lacidofil. CONCLUSIONS: H. pylori infection in gerbils, associated with regenerative hyperplasia of glandular structure, results in the suppression of gastric secretion, overexpression of COX-2, and enhancement in apoptosis and impairment of both, gastric blood flow and gastrin-somatostatin link that were reversed by anti-H. pylori triple therapy and attenuated by probiotics.     

Synergism of Helicobacter pylori infection and stress on the augmentation of gastric mucosal damage and its prevention with alpha-tocopherol

Despite evidence that Helicobacter pylori (H. pylori) infection is closely associated with stress in gastric ulcer patients, the underlying mechanism why ulcer recurrence after stress is augmented especially in patients with H. pylori remains unknown. In this study, we found that oxidative stress played a critical role in the augmented mucosal damage provoked by water immersion restraint stress (WIRS) in H. pylori infection and that an antioxidant, alpha-tocopherol, could ameliorate the aggravation of stress-associated gastric mucosal damage. Two hundred forty SD rats were divided into two groups according to H. pylori inoculation, and after 24 weeks of H. pylori infection, the water immersion restraint stress was imposed for 30, 120, or 480 min, respectively. To evaluate the therapeutic effects of an antioxidant, alpha-tocopherol was administrated 40 mg/kg daily prior to imposing WIRS. Remarkably increased hemorrhagic lesions and bleeding indexes were noted in the H. pylori-infected group with statistical significance (P < 0.05) compared to the noninfected group at the same duration of WIRS. Significantly higher oxidative stress documented by iNOS, lipid peroxides, and GSH level was detected in gastric homogenates of the H. pylori-infected group. Proteomic analysis using 2-dimensional electrophoresis showed a decrease of HSP27 and other chaperone proteins. alpha-Tocopherol pretreatment significantly prevented the gastric mucosal damage, caused by WIRS in the presence of H. pylori. alpha-Tocopherol induced HSP27 expression, which was well correlated with downregulation of iNOS mRNA. Conclusively, the presence of H. pylori caused significant deterioration of stress-induced gastric mucosal lesions through increased oxidative stress and thus antioxidant treatment such as alpha-tocopherol protected the gastric injuries.     

Increased production of matrix metalloproteinases in Helicobacter pylori-associated human gastritis

BACKGROUND AND AIMS: Helicobacter pylori infection results in an active, chronic inflammation of the gastric mucosa. Previous studies have highlighted the importance of matrix metalloproteinases (MMPs) in diseases involving mucosal inflammation, prompting us to investigate MMP activity in H. pylori-induced gastritis. METHODS: Gastric biopsies were obtained from H. pylori-infected and uninfected volunteers, and MMP activity was assessed using substrate gel electrophoresis. MMP production was also evaluated by immunohistochemistry and real time-polymerase chain reaction. In parallel, tissue inhibitors of MMPs (TIMP) levels and TIMP-MMP complexes were examined in corresponding tissues using enzyme-linked immunosorbent assays and Western blotting. Finally, MMP production by gastric macrophages was determined after stimulation with H. pylori. RESULTS: Antral mucosa of H. pylori-infected subjects demonstrated a 19-fold higher MMP-9 activity than that of uninfected individuals. MMP-2 was present at lower levels, but was also increased in H. pylori-infected individuals, while there was no difference in the total levels of TIMP-1 and TIMP-2 between the groups of volunteers. Significant numbers of MMP-9-containing cells were only found in the H. pylori-infected antral mucosa. Tissue-resident macrophages were significantly increased in H. pylori-infected individuals, and double-staining showed MMP-9 colocalized to macrophages. Furthermore, gastric macrophages secreted MMP-9 in response to H. pylori bacteria. A corresponding 10-fold increase of gene expression of MMP-9 was seen in patients infected with H. pylori compared to uninfected individuals. CONCLUSIONS: Helicobacter pylori infection results in a substantial increase in MMP-9 and MMP-2 activity in the gastric mucosa, probably contributed to in large part by tissue-resident macrophages, while no changes were seen in the TIMP levels. The net increase in gastric MMP activity is likely to contribute to tissue damage during H. pylori-associated gastritis.     

Effects of selective cyclooxygenase-2 inhibitor and non-selective NSAIDs on Helicobacter pylori-induced gastritis in Mongolian gerbils

Background. It is still a point of controversy whether Helicobacter pylori‐infected patients are more likely to develop mucosal damage while taking NSADIs. Selective cyclooxygenase (COX‐2) inhibitors may be associated with less severe gastric mucosal damage than conventional NSAIDs, but this association is undefined in H. pylori‐induced gastritis. The aim of this study was to evaluate the effects of selective COX‐2 and nonselective NSAIDs on H. pylori‐induced gastritis. Methods. After intragastric administration of indomethacin, NS‐398 or vehicle alone, once daily for 5 days in H. pylori‐infected and uninfected Mongolian gerbils, we evaluated gastric mucosal damage, inflammatory cell infiltration and prostaglandin E₂ (PGE₂) concentration. We investigated whether H. pylori infection induced the COX‐2 expression. Results. In H. pylori‐uninfected groups, the indomethacin‐treated group showed the highest mucosal damage score and the lowest PGE₂ concentration. There was no difference in mucosal damage scores and PGE₂ concentration between NS‐398 and vehicle‐alone treated group. In H. pylori‐infected groups, there was no difference in mucosal damage scores, irrespective of the type of drugs administered. The indomethacin‐treated group showed the lowest PGE₂ concentration, similar to that of the NS‐398 and vehicle‐alone treated groups, both without H. pylori infection. Gastric neutrophil and monocyte infiltration scores were higher in H. pylori‐infected groups than in uninfected groups. However, there was no difference in these scores according to the type of drugs administered, within H. pylori‐infected or uninfected groups. COX‐2 protein expression was observed in H. pylori‐infected Mongolian gerbils but not in uninfected ones. Conclusions. Our animal study showed that H. pylori infection induced COX‐2 expression and increased prostaglandin concentration. Administration of NSAIDs decreased the prostaglandin concentration, but did not increase mucosal damage in H. pylori‐induced gastritis. Selective COX‐2 inhibitors, instead of conventional NSIADs, had no beneficial effect on preventing mucosal damage in H. pylori‐induced gastritis.     

Reduction of overall Helicobacter pylori colonization levels in the stomach of Mongolian gerbil by Lactobacillus johnsonii La1 (LC1) and its in vitro activities against H. pylori motility and adherence

The effects of Lactobacillus johnsonii La1 (LC1) on Helicobacter pylori colonization in the stomach were investigated. H. pylori colonization and gastritis in LC1-inoculated Mongolian gerbils were significantly less intense than those in the control animals. LC1 culture supernatant (>10-kDa fraction) inhibited H. pylori motility and induced bacterial aggregation in human gastric epithelial cells, suggesting the potential of clinical use of LC1 product.     

Adoptive transfer of splenocytes in SCID mice implicates CD4+ T cells in apoptosis and epithelial proliferation associated with Helicobacter pylori-induced gastritis

Helicobacter pylori causes severe, rapidly progressive gastritis in severe combined immunodeficient (SCID) mouse recipients of congenic splenocytes. The H. pylori-infected and uninfected C57BL/6J and recipient SCID mice were evaluated to detect CD4+ and CD8+ T cells, B cells, apoptotic epithelial cells, and epithelial cell proliferation at postinoculation weeks 5, 6, 8, and 12. Serum was evaluated for anti-H. pylori IgG and IgM. In all H. pylori-infected mice, gastric CD4+ cell scores were increased, compared with scores for uninfected controls. Recipient mice differed, however, according to the source of the transferred CD4+ cells. The CD4+ cell scores for recipients of splenocytes from H. pylori-infected (immune) donors were indistinguishable from those for wild-type donor mice at all time points. In contrast, gastric mucosal CD4+ cell scores did not become significantly high until two weeks after transfer (postinoculation week 6) in recipients of cells from uninfected (na?ve) donors. Gastric epithelial apoptosis and the gastric epithelial proliferation zone were significantly (P < 0.05) increased in infected recipient and donor, compared with non-recipient and uninfected mice at postinoculation week 12. Results indicated that CD4 cells are sensitized in vivo and migrate to the gastric mucosa where they induce gastritis in response to H. pylori antigens. Influx of CD4 cells and gastritis are correlated with epithelial proliferation and apoptosis, and suggest that CD4-dependent H. pylori gastritis leads to epithelial damage with attendant proliferative and metaplastic responses.     

Characteristics of a clinical isolate of urease-negative Helicobacter pylori and its ability to induce gastric ulcers in Mongolian gerbils

BACKGROUND: We clinically obtained urease-negative mutant strains of Helicobacter pylori. The goal of this study was to investigate the ability of the urease-negative strain to colonize and subsequently damage the gastric mucosa in Mongolian gerbils. In addition, the genes encoding the urease production in the test strain were analyzed, and other genes encoding the virulence factors, cytotoxin-associated protein and vacuolating-cytotoxin were evaluated. MATERIALS AND METHODS: The character of urease-negative isolates of H. pylori was defined. The identification of H. pylori was confirmed by polymerase chain reaction (PCR). The H. pylori isolate was transfected into Mongolian gerbils as previously described, which were followed up to 42 weeks, and the changes in their gastric mucosa were examined histologically. RESULTS AND CONCLUSION: Fifteen Mongolian gerbils orally infected with 10(7) colony forming units of urease-negative H. pylori were killed at 4, 12, 24, 36 and 42 weeks (n = 3) after infection. Culture medium without urease-negative H. pylori was given to the Mongolian gerbils as control. H. pylori continued to exist in the subject's stomach and gastric ulceration was observed and compared with the control. Clinically obtained urease-negative H. pylori continued to exist for at least 42 weeks in the subject's stomach and it induced gastric ulcers. These data demonstrated that the urease in H. pylori was not a necessary factor in the formation of gastric ulcers in the Mongolian gerbil model.     

Low concentrations of zinc in gastric mucosa are associated with increased severity of Helicobacter pylori-induced inflammation

BACKGROUND: Chronic Helicobacter pylori infection is the most common cause of gastric cancer. H. pylori induces oxidative stress while zinc deficiency results in increased sensitivity to it. In Ecuador, the prevalence of gastric cancer and zinc deficiency are high. We hypothesized that zinc deficiency in Ecuadorian people would cause increased H. pylori-induced inflammation in the gastric mucosa associated with lower tissue zinc concentrations. METHODS: Three hundred and fifty-two patients with dyspepsia underwent endoscopy to obtain gastric mucosa biopsies. Diagnosis of H. pylori infection and its severity, histopathology, mucosal zinc concentration, and inflammation intensity were determined. RESULTS: H. pylori-infected patients with non-atrophic chronic gastritis had lower concentrations of zinc in gastric mucosa than uninfected patients with the same type of gastritis (251.3 +/- 225.3 vs. 426.2 +/- 279.9 ng/mg of protein; p = .016). Considering all patients, the more severe the H. pylori infection, the higher the percentage of subjects with infiltration by polymorphonuclear (PMN) cells (p = .0001). Patients with high PMN infiltration had lower mucosal zinc concentrations than patients with low PMN infiltration (35.2 +/- 20.7 vs. 242.9 +/- 191.8 ng/mg of protein; p = .021). CONCLUSIONS: The degree of inflammation in H. pylori-induced gastritis appears to be modulated by gastric tissue zinc concentrations.     

幽门螺杆菌感染蒙古沙鼠胃部菌群改变及病理学变化

目的观察蒙古沙鼠感染幽门螺杆菌（Helicobacter pylori,H.pylori）后胃部菌群及病理学变化。方法 5周龄蒙古沙鼠60只,随机分为实验组（30只）和对照组（30只）。所有沙鼠禁食不禁水24 h后,实验组灌喂109CFU/mLH.pylori菌液0.5 mL/只,连续3次。对照组灌喂无菌肉汤。在4、8、16、24和48周处死动物,进行胃部菌群分析和H.pylori分离培养及病理学检查。结果正常沙鼠胃中存在着以乳酸菌为主的正常菌群[（8.43±5.21）×105CFU/g],感染H.pylori后正常菌群数量显著减少;实验组沙鼠H.pylori感染率为100%,第4周可见沙鼠胃组织红肿充血,第8周有炎性细胞浸润,16周和24周出现糜烂,48周见出血、慢性活动性胃炎及溃疡。对照组沙鼠无H.pylori定植及组织学病变。结论 H.pylori感染使蒙古沙鼠胃内正常菌群发生变化,从而引起胃炎和胃溃疡发生。     

Gastric mucosal changes induced by long term infection with Helicobacter pylori in Mongolian gerbils: effects of bacteria eradication

Helicobacter pylori infection has been reported to induce various mucosal changes, including gastric adenocarcinoma, in Mongolian gerbils 62 weeks after inoculation. Using Mongolian gerbils, this study examined whether or not eradication of the bacteria with drugs at specified times after infection prevents the development of mucosal changes. After orally inoculating with H. pylori (TN2GF4, vacA- and cagA-positive), the animals were killed 18 months later. Four or 8 months after H. pylori inoculation, eradication was performed by concurrent treatment with omeprazole+clarithromycin. Immediately after treatment ended, in both the 5 and 9 month groups, it was verified that H. pylori was completely eradicated. Autopsy performed 18 months after H. pylori inoculation revealed gastric hyperplastic polyps with erosive lesions and ulcers that were grossly visible in the non-treated control group. In addition, atrophic gastritis, intestinal metaplasia, carcinoids, and adenocarcinomas were histologically observed in the animals. In animals eradicated after 4 months and autopsied after 18 months, however, such mucosal changes were not observed. In contrast, intestinal metaplasia and mucosal atrophy was observed in animals eradicated after 8 months and autopsied after 18 months. It was concluded that early eradication of H. pylori infection with drug therapy can prevent severe gastric mucosal changes, to include adenocarcinomas, in Mongolian gerbils.