Eradication of Helicobacter pylori significantly reduced gastric damage in nonsteroidal anti-inflammatory drug-treated Mongolian gerbils

AIM: To examine the effect of eradication of Hellcobacter pylori prior to usage of NSAIDs, by investigating gastric inflammatory activity, myeloperoxidase (MPO) activity, prostaglandin (PG) E_2 synthesis in H Pylori-infected, and H pylori-eradicated gerbils followed by administration of indomethacin and rofecoxib. METHODS: Six-week-old male gerbils were orally inoculated with H pylori. Seven weeks later, anti-H pylori triple therapy and vehicle were given to gerbils respectively and followed by oral indomethacin (2 mg/kg·d) or rofecoxib (10 mg/kg·d) for 2 wk. We examined the area of lesions, gastric inflammatory activity, PGE_2 synthesis and MPO activity in the stomach. RESULTS: In indomethacin and rofecoxib-treated gerbils, the following results were obtained in H pylori-infected group vs H pylori-eradicated group respectively: hyperplasia area of the stomach (mm~2): 82.4±9.2 vs 13.9±3.5 (P＜0.05), 30.5±5.1 vs 1.3±0.6 (P＜0.05); erosion and ulcer area (mm~2): 14.4±4.9 vs 0.86±0.5 (P＜0.05), 1.3±0.6 vs0.4±0.3 (P＜0.05); score of gastritis: 7.0±0.0 vs3.6±0.5 (P＜0.05), 7.0±0.0 vs 2.7±0.5 (P＜0.05); MPO activity (μmol H_2O_2/min/g tissue): 104.7±9.2 vs9.0±2.3(P＜0.05), 133.5±15.0 vs2.9±0.7 (P＜0.05); PGE_2 synthesis (pg/mg wet weight/min): 299.2±81.5 vs102.8±26.2 (P＜0.05), 321.4±30.3 vs 11.9±4.8(P＜0.05). CONCLUSION: Eradication of H pylori reduced gastric damage of NSAID-treated Mongolian gerbils. Rofecoxib caused less severe gastric damage than indomethacin in H pylori-eradicated gerbils.     

Development of gastric adenocarcinoma in Mongolian gerbils after long-term infection with Helicobacter pylori

BACKGROUND AND AIM: The experimental evidence that long-term colonization of Helicobacter pylori results in the development of gastric cancer in Mongolian gerbils has been reported only by two Japanese groups to date. This study aimed to investigate the carcinogenicity of H. pylori infection in a Mongolian gerbil model. METHODS: Thirty-six Mongolian gerbils (inner Mongolian origin) were divided into two groups (male to female ratio, 1:1) and orally inoculated with a standard H. pylori strain (ATCC43504) or H. pylori161 (isolated from a Chinese patient with gastric adenocarcinoma), respectively, once a week for 5 weeks. Another 10 control gerbils were given phosphate-buffered saline. The animals were killed 8, 20, 28 and 84 weeks after inoculation for bacterial and histological examination. RESULTS: Seven inoculated gerbils died at the week 42. Overall, H. pylori colonization was detected in 24 (83%) of the 29 available inoculated gerbils. The gastric lesions were aggravated gradually over time. At week 84, moderate to severe gastritis, characterized by diffuse infiltration of mononuclear cells and formation of multiple lymphoid follicles in mucosa and submucosa, and even the lymphoepithelial lesions, were observed. Epithelial hyperplasia were dominant in almost all gerbils. Four (24%) of the 17 animals had hyperplastic polyps. Intestinal metaplasia were rarely seen (in three gerbils). Well-differentiated gastric adenocarcinomas developed in three (18%) of the 17 gerbils after 84 weeks. Of the three gerbils, one female gerbil was infected with H. pylori161 and the others (one male and one female) were infected with ATCC43504. CONCLUSIONS: The present study reconfirms that H. pylori infection alone can induce gastric adenocarcinoma in Mongolian gerbils and suggests that different species of gerbil and both standard and clinically isolated H. pylori strains can be used for investigating the carcinogenesis of H. pylori. This is the first report of the development of gastric cancer in female gerbils, which highlights the importance of using both sexes to investigate the pathogenesis of H. pylori and whether host susceptibility is influenced by sex.     

Inhibition of Helicobacter pylori infection by orally administered yolk-derived anti-Helicobacter pylori antibody

BACKGROUND/AIMS: We studied highly specific chicken egg yolk-derived anti-Helicobacter pylori antibody, and examined efficacy in inducing passive immunity and a bacteriostatic effect on H. pylori. METHODOLOGY: Heat-killed H. pylori were administered orally to hens, and specific anti-H. pylori antibody was purified from the yolk of eggs laid by these hens. The antibody's ability to inhibit H. pylori growth, urease activity, ammonia production, the cytopathic effects, and its effects on serum anti-H. pylori immunoglobulin G (IgG) production were investigated in vitro and in vivo. In addition, H. pylori-infected volunteers received the antibody orally and underwent repeated 13C-urea breath test after antibody ingestion. RESULTS: Anti-H. pylori antibody derived from egg yolk strongly inhibited growth of H. pylori and increased agglutination of H. pylori in vitro. It also strongly inhibited H. pylori-associated urease activity and ammonia production as well as the cytopathic effect of H. pylori on cultured cells. The antibody also inhibited serum anti-H. pylori IgG production and the incidence of acute gastritis in H. pylori-infected Mongolian gerbils. In volunteers, urea breath testing showed decreased urease activity after antibody ingestion. CONCLUSIONS: Anti-H. pylori antibody derived from egg yolk was specific for H. pylori. The antibody had a bacteriostatic effect on H. pylori, inhibited H. pylori urease activity, and inhibited H. pylori infection in Mongolian gerbils and humans.     

Long-term treatment with sterigmatocystin,a fungus toxin,enhances the development of intestinal metaplasia of gastric mucosa in Helicobacter pylori-infected Mongolian gerbils

BACKGROUND: Helicobacter pylori is a human gastric carcinogen. Sterigmatocystin (ST), a fungus toxin, is a risk factor of gastric cancer. Cytotoxin-vacuolation toxin A (VacA) present in supernatants of H. pylori suspensions can cause gastritis and ulcer. The aim of this study was to examine the effects of H. pylori, ST and VacA in Mongolian gerbils. METHODS: Male Mongolian gerbils (n = 196) were treated with H. pylori supernatants (10 ml/1000 mg) mixed with diet or inoculated intragastrically with H. pylori alone or with ST (100 or 1000 ppb), and then killed 27 months later. Gastric tissue sections were stained with haematoxylin and eosin (H&E), periodic acid-Schiff (PAS), Alcian blue (AB, pH 2.5) and with immunostaining for PCNA and p53 expression. RESULTS: In H. pylori-infected gerbils, the normal mucosa was replaced by hyperplastic epithelium. Severe gastritis, cystic dilatation of gastric glands, hyperplastic polyps and intestinal metaplasia were observed. In H. pylori + ST (1000 ppb) gerbils, intestinal metaplasia was significantly more frequent than in H. pylori alone animals. No pathological changes were observed in the H. pylori supernatant group. Osseous metaplasia was observed in the H. pylori + ST (100 ppb) group. Serum gastrin levels of the H. pylori + ST (1000 ppb) group were significantly higher than those of the other groups. PCNA labelling index and p53 index of infected gerbils were significantly higher than those of uninfected groups. CONCLUSION: H. pylori causes gastritis, ulcer and intestinal metaplasia. ST enhances the development of intestinal metaplasia and increases gastrin levels in H. pylori-infected Mongolian gerbils.     

蒙古沙鼠感染幽门螺杆菌后的胃部病理学变化研究

目的　建立幽门螺杆菌 (Helicobacterpylori,Hp)的蒙古沙鼠长期感染模型并观察其胃内的病理学改变。 方法　蒙古沙鼠 (8周龄 ) 80只 ,随机分为实验组 (40只 )和对照组 (40只 ) ,所有沙鼠禁食水 1d ,第 2天灌喂 5 0 %的乙醇 0 3ml,试验组第 3天及第 4天分 3次灌喂cagA Hp菌液 (10 9cfu/ml) ,0 5ml/只·次 ,对照组灌喂相同量无菌肉汤。最后一次灌喂后 2h进食水。距最后一次灌菌后 4、8、12、2 0、2 4周分别剖杀动物 ,每次实验组、对照组各 8只 ,进行微生物学检查 (粘膜涂片染色镜检、分离培养、快速尿素酶试验 )、血清学检查 (ELISA测抗Hp抗体 )和病理学检查。结果　实验组沙鼠在不同时间Hp感染率均达到 10 0 %。从第 4周开始 ,可见所有实验组沙鼠胃组织中有大量炎性细胞浸润 ,随着时间推移形成淋巴滤泡。部分沙鼠在第 12周后至 2 4周可见明显出血、慢性活动性胃炎及溃疡 ,有的溃疡可深达肌层。对照组沙鼠均无Hp定植及组织学病变。结论　蒙古沙鼠感染Hp后 ,可出现与人极相似的病理组织学改变 ,对于研究Hp的致病机制及疫苗具有重要价值     

Duodenogastric reflux and Helicobacter pylori infection synergistically increase gastric mucosal cell proliferative activity in Mongolian gerbils

BACKGROUND: Helicobacter pylori and duodenogastric reflux (DGR) are both recognized as aetiological factors in chronic gastritis and gastric carcinogenesis. In this study, a Mongolian gerbil (MG) model was used to investigate the histopathological changes in the gastric mucosa resulting from DGR and/or H. pylori infection. METHODS: One-hundred-and-eleven 7-week-old, specific-pathogen-free, male MGs were divided into four groups: normal controls, gerbils with surgically induced DGR, and H. pylori-infected gerbils with and without DGR. Gerbils were killed 4, 12 and 26 weeks after DGR surgery, their stomachs removed and sections prepared. Sections were fixed immediately in 20% phosphate-buffered formalin and subjected to haematoxylin and eosin staining, Alcian blue at pH 2.5/periodic acid-Schiff staining, and immunostaining for smooth muscle cells, H. pylori and 5'-bromo-2'-deoxyuridine (BrdU). RESULTS: The gastric mucosa of H. pylori-infected gerbils showed chronic active gastritis irrespective of DGR throughout the experimental period. The gastric mucosa of H. pylori-infected gerbils with DGR demonstrated higher BrdU labelling than in the other groups. CONCLUSIONS: In MGs, DGR and H. pylori infection synergistically increased gastric mucosal cell proliferative activity. DGR and H. pylori infection may be involved synergistically in gastric carcinogenesis by increasing cell proliferative activity.     

蒙古沙土鼠不同幽门螺杆菌菌株感染相关性胃病的研究进展

幽门螺杆菌(Helicobacter pylori,H.pylori)感染在世界范围内高发,他定植于人胃黏膜,导致慢性胃炎及胃癌的发生.蒙古沙鼠(mongolian gerbil,MG)很少患自发性胃炎,且不是H.pylori 的自然宿主.人工接种H.pylori后,蒙古沙鼠患H.pylori相关性胃病与胃病患者最相似...     

H pylori infection causes chronic pancreatitis in Mongolian gerbils

AIM： To investigate whether chronic H pylori infection has the potential to induce pancreatitis in the Mongolian gerbil model, and whether it is dependent on an intact type Ⅳ secretion system. METHODS： Mongolian gerbils were infected with wild type （WT） H pylori type Ⅰ strain B128 or its isogenic mutant B128 △cag γ （defective type Ⅳ secretion）. After seven months of infection, H pylori was reisolated from antrum and corpus and Hpylori DNA was analyzed by seminested polymerase chain reaction （PCR）. Inflammation and histological changes were documented in the gastric antrum, corpus, and pancreas by immunohistochemistry. Cytokine mRNA, gastric pH, plasma gastrin, amylase, lipase, and glucose levels were determined.
RESULTS： The H pylori infection rate was 95%. Eight infected animals, but none of the uninfected group, developed transmural inflammation and chronic pancreatitis. Extensive interstitial fibrosis and inflammation of the pancreatic lobe adjacent to the antrum was confirmed by trichrome stain, and immuno-histochemically. Pro-inflammatory cytokine mRNA was significantly increased in the antral mucosa of all infected gerbils. In the corpus, only cytokine levels of WT-infected animals andthose developing transmural inflammation and pancreatitis were significantly increased. Levels of lipase, but not glucose or amylase levels, were significantly reduced in the pancreatitis group. H pylori DNA was detected in infected antral and corpus tissue,but not in the pancreas
CONCLUSION： H pylori infection is able to induce chronic pancreatitis in Mongolian gerbils independently of the type Ⅳ secretion system, probably by an indirect mechanism associated with a penetrating ulcer.     

Helicobacter pylori strain-specific modulation of gastric inflammation in Mongolian gerbils

AIM: The cag pathogenicity island (PAI) is one of potential virulence determinants of Helicobacter pylori. The Mongolian gerbil is a suitable experimental animal for the screening of virulence factors of H pylori. METHODS: Five-week-old Mongolian gerbils were inoculated with a standard H pylori strain (ATCC 43504) possessing the cag PAI or a clinical isolate lacking the genes' cluster (OHPC-0002). The animals were killed at 2, 4, 8, 24 and 48 wk after inoculation (n=5 each), and macroscopic and histopathological findings in the stomachs were compared. RESULTS: In gerbils infected with ATCC 43504, a more severe degree of infiltration of polynuclear and mononuclear cells and lymphoid follicles was observed from 4 wk after inoculation compared to gerbils infected with OHPC-0002 especially in the antrum and transitional zone from the fundic to pyloric gland area. In addition, glandular atrophy, intestinal metaplasia, gastric ulcer and hyperplastic polyps were noted in gerbils infected with ATCC 43504, whereas only mild gastric erosions occurred in those infected with OHPC-0002. CONCLUSION: Our results indicate that the cag PAI could be directly involved in gastric immune and inflammatory responses in the Mongolian gerbils, leading to a more advanced gastric disease.     

Comparative Analysis of Colonization of Helicobacter pylori and Glycolipids Receptor Density in Mongolian Gerbils and Mice

The Mongolian gerbil has been used as an excellent experimental animal model for studying Helicobacter pylori infection because it can stably colonize and induce severe chronic gastritis, ulceration, and cancer-simulating human diseases in this animal. In contrast, H. pylori can only induce mild inflammation in many mouse models. The aim in this study is to clarify the difference of induction of pathological lesions in the two animal models. SPF ICR mice and Mongolian gerbils were inoculated with a clinically isolated strain of H. pylori. Six weeks after inoculation, bacteria colonizing the stomach were counted. Immunohistochemical staining and biochemical analyses of three putative receptor glycolipids were performed with monoclonal antibodies to the respective glycolipids. Significantly higher numbers of H. pylori were recovered from the stomachs of Mongolian gerbils than mice (5.77 ± 0.46 log CFU vs 4.17 ± 0.55 log CFU, P < 0.01). Immunohistochemical studies showed that sulfatide expression in the gastric mucosa of Mongolian gerbils was much stronger than that in mice, whereas the expression of Lewis^b glycolipid and GM3 were almost equal. Quantitative analysis of each glycolipid by thin-layer chromatography confirmed the results of immunohistochemical study, showing 4.1 times higher sulfatide content in the Mongolian gerbil stomach. The content of both Lewis^b and GM3 was almost equivalent in these two animals. In conclusions, higher levels of sulfatide expression, a putative adhesion receptor, in the gastric mucosa of Mongolian gerbils may allow abundant colonization by H. pylori, resulting in the development of gastric lesions in this animal model.     

Ethanol intake preceding Helicobacter pylori inoculation promotes gastric mucosal inflammation in Mongolian gerbils

BACKGROUND: Mongolian gerbils have been reported to be a suitable model for Helicobacter pylori-associated gastric mucosal injury, including gastric cancer. Although ethanol is known to be one of the harmful substances in the gastric mucosa, the relationship between ethanol and H. pylori infection remains unknown. The aim of the present study is to investigate the effect of ethanol treatment prior to H. pylori inoculation on associated gastric mucosal injury. METHODS: Male Mongolian gerbils were used for the study. Helicobacter pylori was orally inoculated after 15 h fasting (Hp group). Thirty minutes prior to H. pylori inoculation, a group of gerbils was orally treated with 40% ethanol (20 mL/kg; E + Hp group). Another group of animals was treated either with H. pylori culture media alone (controls) or with 40% ethanol plus culture media (E group). Gerbils were killed 2, 4 or 12 weeks after H. pylori inoculation. Helicobacter pylori infection was confirmed by both histological examination and serological tests. Mucosal damage was evaluated histologically according to the modified Sydney system. RESULTS: Although in the controls and E group no significant change to the gastric mucose was observed, persistent H. pylori infection was seen in the mucosa and mucosal leucocyte infiltration and severe epithelial damage was observed in the Hp and E + Hp groups after 4 weeks. The histological scores for polymorphonuclear cell infiltration and myeloperoxidase activity were higher in the E + Hp group at 4 weeks than in the Hp group (P < 0.05). CONCLUSIONS: Ethanol intake preceding H. pylori inoculation could promote the progression of gastric mucosal inflammation in Mongolian gerbils.     

Role of N-methyl-N-nitrosourea in the induction of intestinal metaplasia and gastric adenocarcinoma in Mongolian gerbils infected with Helicobacter pylori

BACKGROUND: Progression from intestinal metaplasia to neoplasia has not been demonstrated experimentally. The hypothesis that gastric adenocarcinoma arises from intestinal metaplasia was tested in a Mongolian gerbil model of Helicobacter pylori (H. pylori) infection. METHODS: One hundred and fourteen specific pathogen-free gerbils were divided in five groups. A and D: infected with H. pylori and administered the carcinogen N-methyl-N-nitrosourea (MNU); C and E: received MNU; B: H. pylori, but no MNU. Animals were killed at 41 weeks, stomachs were mapped, and the relationship between metaplasia and cancer was assessed. RESULTS: Intestinal metaplasia occurred more frequently in the H. pylori-infected, MNU-treated gerbils than in those receiving H. pylori inoculation only (P < 0.01). Carcinomas arose only in H. pylori-infected animals receiving MNU (8 well differentiated, 2 poorly differentiated, and 10 signet ring). Intestinal metaplasia occurred more frequently in association with intestinal-type carcinoma. CONCLUSIONS: Intestinal metaplasia and adenocarcinoma arise in stomachs subjected to the same injuries (in this study, H. pylori and MNU). Only two intestinal-type carcinomas were contiguous to intestinal metaplasia; all other tumors developed most commonly at non-metaplastic sites. This suggests that in this animal model H. pylori and MNU induce several phenotypes of gastric cancer, but intestinal metaplasia may be a direct precursor only in a subset of the intestinal-type tumors.     

幽门螺杆菌长期感染蒙古沙土鼠腺胃模型的建立及评价

目的 建立幽门螺杆菌（Helicobacter pylori,Hp）长期感染蒙古沙土鼠腺胃模型,验证该模型出现的病理改变及腺胃肿瘤的发生情况。方法 采用国际标准菌株NCTC 11637灌喂蒙古沙土鼠,建立HP长期感染蒙古沙土鼠腺胃模型。结果 成功建立了HP长期感染蒙古沙土鼠腺胃模型,其胃黏膜的组织学变化显示,HP感染可致正常胃黏膜→慢性胃炎→萎缩→肠化生→异型增生的发展过程,Hp NCTC 11637定植于蒙古沙土鼠腺胃65财哩,可引起胃黏膜出现严重的萎缩、肠化生及不典型增生等胃癌前状态,暂未发现早期癌。结论 Hp NCTC 11637易长期定植于蒙古沙土鼠腺胃,模型的稳定性及重复性极佳,且与Hp感染人胃黏膜后出现的各种病理变化极为相似。     

蒙古沙鼠感染幽门螺旋杆菌后胃黏膜细胞因子水平的改变

目的探讨幽门螺旋杆菌感染后胃黏膜重要细胞因子的改变，为免疫治疗提供理论依据。方法制作幽门螺旋杆菌感染蒙古沙鼠的动物模型，感染6周后处死动物，证实幽门螺旋杆菌定植成功，以RT—PCR方法检测胃黏膜IFN-γ、IL-12、IL-18的水平。结果幽门螺旋杆菌感染组IFN／G3PDH、IL-12／G3PDH分别为1．19±0．86、1．85±0．96，高于对照组；感染组和对照组之间IL-18／G3PDH无显著性差异。结论 IFN-1、IL-12水平的改变可能参与了幽门螺旋杆菌的致病过程。     

Helicobacter pylori infection potentiates aspirin induced gastric mucosal injury in Mongolian gerbils

BACKGROUND: Helicobacter pylori infection and non-steroidal anti-inflammatory drugs are two major causes of gastric ulceration but interactions between H pylori and these drugs in gastric mucosal injury are unclear. AIMS: We studied the influence of experimental H pylori infection on gastric mucosal injury induced by aspirin. SUBJECTS: Male Mongolian gerbils free of specific pathogens were used. METHODS: H pylori ATCC43504 culture broth was administered by oral gavage at seven weeks of age. After three weeks, acidified aspirin (400 mg/kg) was administered orally, and three hours later the total area of gastric erosions, myeloperoxidase (MPO) activity (an index of neutrophil accumulation), thiobarbituric acid reactive substances (TBARS, an index of lipid peroxidation), and KC/GRO (a chemoattractive cytokine in rodents) were measured in gastric mucosa. To determine the role of neutrophils in these circumstances, antigerbil neutrophil rabbit serum (ANS) was administered to some animals 18 hours before aspirin. RESULTS: Aspirin caused more extensive haemorrhagic erosions (33.1 (12.3) mm2) associated with greater MPO activity (1887.7 (598.5) microU/mg protein) and TBARS (0.33 (0.14) nmol/mg protein) and KC/GRO concentrations (28.3 (9.5) pg/mg protein) in infected than in uninfected gerbils (13.7 (2.3); 204.0 (68.9); 0.12 (0.06); 3.1 (0.8), respectively) Pretreatment with ANS inhibited the increases in gastric erosions, MPO activity, and TBARS but not KC/GRO concentration. The reduction in aspirin induced mucosal injury by administration of ANS was much greater in H pylori infected animals (65%) than in uninfected animals (31%). CONCLUSIONS: H pylori infection potentiates aspirin induced gastric mucosal injury by mechanisms that include accumulation of activated neutrophils.     

Helicobacter pylori infection induces duodenitis and superficial duodenal ulcer in Mongolian gerbils

BACKGROUND: There is no direct evidence for an animal model of Helicobacter pylori induced duodenal ulcer. AIM: In this study we evaluated the roles of bacterial strain and age of experimental animals in induction of duodenitis and duodenal ulcer in Mongolian gerbils after H pylori infection. METHODS: Specific pathogen free Mongolian gerbils were inoculated orally with three bacterial strains (H pylori ATCC 43504, TN2GF4, and K-6, a clinical isolate from a patient with gastric cancer in our clinic). These strains have both the cagA gene and VacA. Five week old gerbils were used to emulate prematurity infection and 14 week old animals were used as mature test subjects. Animals were observed for 12 weeks after inoculation. Interleukin 8 (IL-8) production in gastric epithelial cells (MKN74) after coculture with the H pylori strains was measured by ELISA. RESULTS: Gastritis and gastric ulcers were found in all gerbils infected with the three strains. However, duodenitis and gastric metaplasia were seen more frequently in gerbils infected with TN2GF4 and K-6 strains than in the ATCC 43504 infected or control groups (p<0.05). Superficial duodenal ulcers with severe duodenitis and gastric metaplasia were found in two gerbils inoculated at 14 weeks with the TN2GF4 strain but none at five weeks. The TN2GF4 strain stimulated significantly higher levels of IL-8 than ATCC 43504 and K6 strains (p=0.0039). CONCLUSIONS: When injected into adult Mongolian gerbils, a specific strain (TN2GF4) of H pylori can induce duodenitis with gastric metaplasia and superficial duodenal ulcers. Induction of duodenal ulcer in an animal model fulfills the requirements of Koch's postulates for establishing a role for H pylori as a causative agent.     

Establishment of Helicobacter pylori infection model in Mongolian gerbils

AIM：To establish a stable and reliable model of Helicobacter pyloriinfection model in Mongolian gerbils and to observe pathological changes in gastric mucosa in infected animals.METHODS:Mongolian gerbils were randomly divided into 18 groups;6 groups were infected with Hpylori clinical strain Y06 (n=6, groups Y), 6 groups were infected with Hpylori strain NCTC11637 (n=6, roups N),and 6 uninfected groups as negative controls (n=4,groups C).Hpylori suspensions at the concentrations of 2&#215;10^8 and 2&#215;10^9CFU/mL of strain NCTC11637 and strain Y06 were prepared. The animals in three groups N and in three groups Y were orally challenged once with 0.5 mL of the low concentration of the bacterial suspension.The animals in another three groups N and in another three groups Y were orally challenged with 0.5mL of the high concentration of the bacterial suspension for 3 times at the intervals of 24 h,respectively.For the negative controls,the animals in six groups C were orally given with the same volume of Brucella broth at the corresponding inoculating time.The animals were killed after 2nd, 4^th and 6^th week after the last challenge and the gastric mucosal specimens were taken for urease test,bacterial isolation, pathological and immunohistochemical examinations.RESULTS:Positive isolation rates of Hpyloriin the animals of groups Y at the 2nd, 4^th and 6^th week after one challenge were 0%, 16.7% and 66.7%, while in the animals of groups N were 0%, 0% and 16.7%, respectively.Positive isolation rates of Hpyloriin the animals of groups Y at the 2nd, 4^th and 6^th week after three challenges were 66.7%,100% and 100%,while in the animals of groups N were 66.7%,66.7% and 100%, respectively. In animals with positive isolation of Hpylori, the bacterium was found to colonized on the surface of gastric mucosal cells and in the gastric pits,and the gastric mucosal lamina propria was infiltrated with inflammatory cells.CONCLUSION:By using H pylori suspension at high concentration of 2&#215;10^9 CFU/mL for multiple times,the orally challenged Mongolian gerbils can be used as a stable and reliable H pylori infection model.The 2 strains of H pylori can colonize in gastric mucosa of the infected animals and cause mild inflammation reaction.     

Functional and morphological aspects of Helicobacter pylori-induced gastric cancer in Mongolian gerbils

BACKGROUND: Helicobacter pylori infection of Mongolian gerbils is an established model of gastric carcinogenesis, but gastric secretory aspects of this carcinogenesis have not been studied. METHODS: The effects of single intragastric inoculation of gerbils with H. pylori strain (cagA+ vacA+, 5 x 10(6) CFU/ml) or vehicle (saline) were examined at 1, 2, 4, 6, 9, 12 and 30 weeks from inoculation. Gastric morphology, the presence of H. pylori using the rapid urease test, the density of H. pylori and 16S rRNA and the plasma gastrin and somatostatin were determined. RESULTS: H. pylori was detected in gastric mucosa in all infected animals. Basal gastric acid in gerbils was reduced by about 50% after H. pylori inoculation. Early lesions seen at 4 weeks after H. pylori inoculation consisted of chronic gastritis with thickened mucosal folds, oedema, congestion and mucosal lymphocytic infiltration. Adenomatous hyperplasia with cellular atypia with increased mitotic activity and the formation of apoptotic bodies and visible erosions and ulcerations were observed at 12-30 weeks after inoculation. The atypical gastric glands were situated 'back-to-back', suggesting gastric pre-cancer. The gastric blood flow in H. pylori-infected gerbils was significantly lower than that in the controls. Six- to seven-fold increase in plasma gastrin levels combined with significant fall in gastric somatostatin contents and the intraepithelial neoplasia were noticed in gerbils at all tested periods. CONCLUSION: H. pylori-infection in gerbils resulted in gastric pre-cancer associated with functional changes, such as suppression of gastric secretion and impairment of both gastric mucosal microcirculation and the gastrin-somatostatin link.