幽门螺杆菌致病机制的研究进展

幽门螺杆菌(Hp)感染与多种消化系统疾病密切相关.许多细菌在致病过程中,首先对其合适的宿主寄生部位进行趋化和定植,最后致病.此文从Hp的定向趋化黏附、定植和毒力几个方面就Hp致病机制的研究进展进行简要综述.     

幽门螺杆菌感染在口腔内科疾病的研究进展

幽门螺杆菌是人类感染率较高的革兰氏阴性菌,可引起胃部疾病,也与口腔疾病相关。幽门螺杆菌传播途径、致病机制使其极易诱发口腔疾病,研究发现幽门螺杆菌与牙周病、口腔黏膜病等口腔疾病有着密切的联系。牙周袋可被视为Hp定植的潜在危险因素,牙菌斑也可能是幽门螺杆菌的庇护所。因此,Hp感染的治疗必须同时进行局部口腔治疗。     

幽门螺杆菌及其感染的诊断

在西方国家大约30%～50%的人群感染有Hp.在我国感染率更高,普通人群Hp感染率达50%～60%,并有报道指出人群感染Hp的比例随年龄增长而提高.自从1983年Warren等人首次发现Hp以来,国内外有关Hp的研究甚快,Hp现已被公认为上消化道疾病的重要致病因素.经胃黏膜组织样品培养及针对性治疗确证,Hp是慢性活动性胃炎的病原茵,也是消化性溃疡的重要致病因子.     

胆汁反流性胃炎的病因分析

目的:探讨胆汁反流性胃炎的病因,及其与幽门螺杆菌(Hp)致病的相关性.方法 :对216例经内镜检查和病理证实的胆汁反流性胃炎患者的病因进行分析,并行幽门螺杆菌检测.结果 :216例胆汁反流性胃炎患者的病因有胃切除术史86例,胆结石、胆囊炎者63例,糖尿病史者24例,消化性溃疡8例,肝炎、肝硬化7例,消化道肿瘤7例,胰腺炎3例,不明原因者18例.胆汁反流性胃炎患者中Hp感染率不高(26.9%).结论 :胆汁反流性胃炎与胃切除术、胆囊疾病、糖尿病、消化性溃疡、胰腺炎、肝炎、肝硬化、消化道肿瘤相关.就胃炎而言,胆汁反流和Hp感染是2个独立的致病因子.胆汁反流与幽门螺杆菌(Helicobacter pylori,Hp)都是慢性胃炎的常见致病因素,动物实验还证实两者均有一定的致癌作用,但是,胆汁反流及Hp对致炎症、致肿瘤作用的关系并不十分清楚.本文对数年来我院诊治的216例胆汁反流性胃炎进行病因分析,并初步探讨胆汁与Hp对胆汁反流性胃炎的致病关系.     

幽门螺杆菌感染对结直肠癌发生的相关因素分析

目的 探讨幽门螺杆菌(Hp)感染对结直肠癌发生的相关因素,为预防结直肠癌发生提供依据.方法 将选取的60只清洁级雄性Wistar幼年大鼠随机分为4组,第1组为单纯Hp组,用Hp菌灌胃法定植Hp;第2组单纯N-甲基亚硝基脲(MNU)组用Hp菌液等量布氏肉汤灌喂,10周后用MNU灌肠诱发结直肠癌形成；第3组采用Hp+ MNU联合处理定植Hp基础上,10周后用MNU灌肠诱发结直肠癌形成；第4组用与Hp菌液等量布氏肉汤灌喂基础上用MNU等量去离子水经肛门灌肠,定期处死大鼠后提取标本,检测Hp,同时做病理切片标本,观察有无肠壁增厚、肠黏膜充血、水肿、糜烂、溃疡及结节发生.结果 Hp组及Hp+ MNU组大鼠较MNU组、第4组胃黏膜明显偏薄,以胃窦部较为明显,且可见肠上皮化生；Hp组及Hp+ MNU组共定植28只小鼠,尿素酶染色阳性21只,培养阳性17只,Giemsa染色阳性达23只,两项阳性大鼠共有25只,占总定指数89.3％.结论 长期的Hp感染可能会增加大鼠结直肠癌对致癌剂的敏感性,促进结直肠癌病变形成,而血胃泌素在结直肠癌的发生过程中是诱导机制之一.     

含抗幽门螺杆菌特异性抗体牛奶清除效果的动物实验研究

目的研究含抗幽门螺杆菌特异性抗体牛奶对感染幽门螺杆菌(Hp)的小鼠动物模型Hp的清除作用,为含抗Hp特异性抗体牛奶的临床应用提供依据。方法实验组对感染Hp的小鼠模型每日经口喂饲含有抗Hp特异性抗体的牛奶0.5 ml进行治疗,治疗周期20 d,以生理盐水和普通牛奶治疗作为对照组;治疗后取鼠胃进行尿素酶实验,组织学检查和胃组织的Hp定植细菌密度检测;统计分析用SPSS13.0软件完成。结果治疗后,含抗Hp抗体牛奶组尿素酶实验6例阳性,9例阴性;Hp细菌培养9例Hp完全根除,6例部分根除,胃组织Hp的定植密度为103-5CFU/g胃组织;与生理盐水组和普通牛奶组比较差异有统计学意义(P0.05)。结论含抗Hp特异性抗体的牛奶能够对部分感染Hp的小鼠模型完全根除Hp感染,对不根除Hp感染者,也有明显的杀灭作用。     

幽门螺杆菌和维生素C与胃黏膜病变关系的研究

目的 研究Hp感染和胃液中维生素C浓度与胃黏膜病变的关系,探讨Hp致病、致癌机制.方法 用高铁还原法测定胃液中维生素C浓度,用快速尿素酶试验、病理Giemsa染色和细菌培养检测Hp.对部分Hp阳性的胃部良性病变患者进行Hp根除治疗,并比较治疗前后胃液中维生素C浓度的变化.结果 Hp阳性各胃部病变组患者胃液中维生素C浓度分别为:慢性浅表性胃炎组(18.3±4.5)mg/L、萎缩性胃炎伴肠上皮化生组(9.1±3.3)mg/L、异型增生组(8.2±2.7)mg/L、胃癌组(5.2±1.6)mg/L,与对照组[(35.2±7.2)mg/L]比较差异均有统计学意义(P＜0.05);经Hp根除治疗后,Hp根除患者胃液中维生素C浓度恢复正常,而Hp未根除患者其胃液中维生素C浓度治疗前后无明显变化.结论 Hp感染可导致胃液中维生素C浓度降低,这可能是Hp致病、致癌机制之一;根除Hp可以恢复胃液中维生素C浓度,这有利于预防胃癌的发生.     

消化道疾病患者幽门螺杆菌感染情况分析

幽门螺杆菌(Helicobacter pylori,Hp)是消化性溃疡、慢性胃炎等消化系统疾病的重要致病因子,也是世界卫生组织确定的胃癌Ⅰ类致癌原[1].中国是Hp高感染国家,不同地区人群感染率差异明显.明确Hp感染的流行病学特点,对防治Hp相关疾病有重要作用.为了解陕西省宝鸡市消化道疾病患者Hp感染状况,本研究选取宝鸡市人民医院2010年1-10月门诊及住院收治的消化道疾病患者,进行了Hp感染状况调查.现将结果报告如下.     

非甾体类消炎药物与幽门螺杆菌感染对上消化道溃疡协同致病作用研究

目的探讨幽门螺杆菌(Hp)感染和非甾体类消炎药(NSAIDs)对上消化道溃疡的协同致病作用,为临床治疗消化道溃疡提供理论指导。方法选取消化科于2014年3月-2015年3月收治的200例消化道溃疡患者作为观察组,将同期就诊的200例非消化道溃疡患者作为对照组,对两组患者Hp感染和服用NSAIDs进行调查,并分析其对上消化道溃疡的协同致病作用。结果 Hp感染服用NSAIDs的患者患胃溃疡的OR值明显比仅感染Hp者和仅服用NSAIDs者患胃溃疡之和高,差异有统计学意义(P<0.05);Hp感染服用NSAIDs对十二指肠溃疡和胃溃疡患者,引发上消化道出血的OR值均明显比仅感染Hp者和仅服用NSAIDs者,引发上消化道出血的OR值之和低,差异有统计学意义(P<0.05)。结论 Hp感染和NSAIDs对胃溃疡具有协同致病作用;而在溃疡合并上消化道出血中无协同致病作用;溃疡合并上消化道出血和服用NSAIDs的时长无关。     

非甾体类消炎药物与幽门螺杆菌感染对上消化道溃疡协同致病作用研究北大核心CSCD

目的探讨幽门螺杆菌(Hp)感染和非甾体类消炎药(NSAIDs)对上消化道溃疡的协同致病作用,为临床治疗消化道溃疡提供理论指导。方法选取消化科于2014年3月-2015年3月收治的200例消化道溃疡患者作为观察组,将同期就诊的200例非消化道溃疡患者作为对照组,对两组患者Hp感染和服用NSAIDs进行调查,并分析其对上消化道溃疡的协同致病作用。结果 Hp感染服用NSAIDs的患者患胃溃疡的OR值明显比仅感染Hp者和仅服用NSAIDs者患胃溃疡之和高,差异有统计学意义(P<0.05);Hp感染服用NSAIDs对十二指肠溃疡和胃溃疡患者,引发上消化道出血的OR值均明显比仅感染Hp者和仅服用NSAIDs者,引发上消化道出血的OR值之和低,差异有统计学意义(P<0.05)。结论 Hp感染和NSAIDs对胃溃疡具有协同致病作用;而在溃疡合并上消化道出血中无协同致病作用;溃疡合并上消化道出血和服用NSAIDs的时长无关。     

Immunization with recombinant Helicobacter pylori urease decreases colonization levels following experimental infection of rhesus monkeys

Rhesus monkeys, naturally colonized with H. pylori as indicated by culture and histology were immunized with either 40 mg recombinant H. pylori urease administered orally together with 25 microg Escherichia coli heat-labile enterotoxin (LT) or immunized with LT alone. An initial 6 doses were administered over an 8 week period. All five vaccinated monkeys had a greater than two-fold rise in urease-specific serum IgG and IgA level and urease-specific salivary IgA was induced in 3 of 5 vaccinated animals after 6 or 7 doses of vaccine. Vaccination had no measurable therapeutic effect on H. pylori colonization. H. pylori was eradicated from these monkeys with a course of antimicrobials plus omeprazole, a 7th vaccine dose was given (10 months after the 6th dose) and they were rechallenged with H. pylori. Necropsy was performed 23 weeks after rechallenge and H. pylori colonization was determined by histological examination of 12 individual gastric sites. A significant reduction in colonization (p < or = 0.0001; Friedman's analysis of variance) was found in the vaccinated animals. Histopathologic examination of necropsy tissues also revealed a trend towards reduced gastritis and epithelial alterations in the vaccinated group compared to animals receiving LT alone. This study provides the first evidence for effective vaccination of nonhuman primates against H. pylori, and preliminary evidence that a reduction in bacterial density attributable to immunization may lessen gastric inflammation.     

Effect of the ingestion of a dietary product containing Lactobacillus johnsonii La1 on Helicobacter pylori colonization in children

OBJECTIVES: Dietary components such as vegetable or probiotic microorganisms have been proposed as an alternative solution to decrease Helicobacter pylori colonization in at-risk populations. Some strains of lactic acid bacteria have been shown to exert bacteriostatic or bactericidal effects against H. pylori in in vitro and in vivo models of infection by this pathogen. We investigated whether regular ingestion of a dietary product containing Lactobacillus johnsonii La1 or L. paracasei ST11 would interfere with H. pylori colonization in children. METHODS: A double blind, randomized, controlled clinical trial was carried out in school children from a low socioeconomic area of Santiago. Subjects were 326 asymptomatic children (9.7 +/- 2.6 y) screened for H. pylori by the (13)C-urea breath test; H. pylori-colonized subjects were distributed into five groups to receive a product containing live La1 or ST11 (groups 1 and 3), heat-killed La1 or ST11 (groups 2 and 4), or vehicle (group 5) everyday for 4 wk. A second (13)C-urea breath test was carried out at the end of this period. Differences in delta(13)CO(2) above baseline values before (DOB1) and after (DOB2) probiotic treatment were evaluated. RESULTS: A high prevalence of H. pylori colonization, 77.3%, was observed in our population. A moderate but significant difference (DOB2 - DOB1) was detected in children receiving live La1 (-7.64 per thousand; 95% confidence interval, -14.23 to -1.03), whereas no differences were observed in the other groups. The magnitude of the decrease in DOB values induced by La1 ingestion correlated with the basal values of DOB before treatment (r = 0.48, P = 0.0074). CONCLUSIONS: Regular ingestion of a product containing Lactobacillus La1 may represent an interesting alternative to modulate H. pylori colonization in children infected by this pathogen.     

Helicobacter pylori and overweight status in the United States: data from the Third National Health and Nutrition Examination Survey

Obesity is an important public health problem in the United States. Because of its potential effects on gastric leptin homeostasis, Helicobacter pylori may play a role in regulating body weight. The authors' aim in this study was to examine the association between H. pylori colonization and overweight status. Nonpregnant participants in the Third National Health and Nutrition Examination Survey (1988-1994) aged > or = 20 years who had had H. pylori testing performed and body mass index (weight (kg)/height (m2)) measured were studied. Overweight was defined as a body mass index greater than or equal to 25. On the basis of serologic results, the participants were categorized into three H. pylori status groups: H. pylori-positive and cytotoxin-associated gene A (cagA)-positive (H. pylori+ cagA+), H. pylori-positive and cagA-negative (H. pylori+ cagA-), and H. pylori-negative (H. pylori-). Of the 7,003 subjects with complete body mass index and H. pylori data, 2,634 (weighted percentage, 22.9%) were H. pylori+ cagA+, 1,385 (15.1%) were H. pylori+ cagA-, and 2,984 (62.0%) were H. pylori-. The adjusted odds of being overweight were 1.17 (95% confidence interval: 0.98, 1.39; p = 0.075) for the H. pylori+ cagA+ group and 0.99 (95% confidence interval: 0.80, 1.22; p = 0.92) for the H. pylori+ cagA- group in comparison with H. pylori- subjects. Serum leptin levels did not differ significantly between the three H. pylori groups. In this US population-based study, there was no significant association between H. pylori colonization, cagA+ strains of H. pylori, and being overweight.     

Relation between Helicobacter pylori cagA status and risk of peptic ulcer disease

Although colonization with any Helicobacter pylori strain is associated with peptic ulcer, it is uncertain whether the risk is greater with cagA(+) or cagA(-) strains, which differ in their biology. A nested case-control study was done, based on a cohort of 5,443 Japanese-American men examined on the Hawaiian island of Oahu from 1967 to 1970. A total of 150 men with gastric ulcer, 65 with duodenal ulcer, and 14 with both diseases were identified. The authors matched the 229 cases with 229 population controls and tested their serum for immunoglobulin G antibodies to H. pylori and immunoglobulin G antibodies to the cagA product of H. pylori using enzyme-linked immunosorbent assays. Persons with H. pylori positivity had an odds ratio of 4.0 (95% confidence interval (CI): 1.9, 8.5) for gastric ulcer and 2.5 (95% CI: 0.8, 7.4) for duodenal ulcer. For CagA positivity, the odds ratios were 1.4 (95% CI: 0.9, 2.4) for gastric ulcer and 2.6 (95% CI: 1.1, 5.8) for duodenal ulcer. Subjects who were seropositive for both H. pylori and CagA had an odds ratio of 4.4 (95% CI: 1.8, 10.5) for gastric ulcer and 5.8 (95% CI: 1.1, 30.0) for duodenal ulcer. The results suggest that colonization with a cag(+) H. pylori strain elevates the risk beyond that of a cag(-) H. pylori strain for both gastric and duodenal ulcers.     

调节性T细胞在幽门螺杆菌感染相关疾病中的作用

幽门螺杆菌(Hp)感染可诱导强烈的先天性免疫和特异性免疫应答。然而,如果未经治疗,Hp感染不会消失,慢性活动性胃炎将会持续进展。胃炎的局部状态及其免疫应答是细菌持续存在的主要原因和最终的临床结果 。调节性T细胞在Hp感染中作用已经有许多争议,它可抑制机体对Hp的免疫应答,从而减轻急性炎症的发生,但同时也造成Hp在胃黏膜中的长期定植,从而使慢性感染持续存在,导致病变的进一步发展。现将调节性T细胞在Hp感染的不同临床表现中的作用作一综述。     

幽门螺杆菌Vac A基因m1b变异体的序列特点及其空泡毒素表达活性

目的调查分析来自浙江人群的Hp临床菌株Vac A基因m1b变异体的序列特点及其空泡毒素表达活性.方法取Hp临床菌株及标准菌标培养于改良的布氏肉汤,在倒置显微镜下观察空泡变性的细胞数.结果 Vac A基因存在于所有Hp菌株中,但只有部分菌株有空泡毒活性,其表达差异与Vac A基因型的不同有关,本研究中m2和 m1b型Hp菌株占优势,而m1型少见.结论 m1b型比m2型菌株更适于在人群定植.     

Oral immunization with HpaA affords therapeutic protective immunity against H. pylori that is reflected by specific mucosal immune responses

In the present study, we evaluated the capacity of Helicobacter pylori adhesin A (HpaA), a H. pylori specific colonization factor, to induce therapeutic protection against H. pylori infection in mice. We found that oral immunization of H. pylori infected mice with HpaA induced protection, i.e. significant reduction in bacterial load in the stomach. This was even more pronounced when a combination of HpaA and urease was used. The protection was strongly related to specific mucosal CD4+ T cell responses with a Th1 profile as well as to mucosal IgA responses locally in the stomach. These findings suggest that HpaA is a promising vaccine candidate antigen for use in a therapeutic vaccine against H. pylori.     

Well water--one source of Helicobacter pylori colonization

Helicobacter pylori (H. pylori) is one of the world's most widespread microorganisms. Its acquisition in humans remains poorly understood, however, epidemiological studies have identified drinking water as reservoir for the bacterium. The aim of this study was to investigate the prevalence of H. pylori infection among individuals using or drinking previously H. pylori tested well water. Applying household cluster sampling, a total of 91 subjects, all using or drinking well water (13 of either H. pylori positive or negative wells), were screened for their H. pylori status. The group was comprised of 73 adults and 19 children under the age of 18. H. pylori infection was determined using the [13C]urea breath test. A self-administered or parent-completed questionnaire provided information on living conditions and lifestyle habits including the use or drinking of well water. Logistic regression analyses associated the drinking of H. pylori positive well water with a positive colonization status [Odds Ratio (OR) 8.3; 95% confidence interval (95% CI) 2.4-29]. In summary, the use or drinking of H. pylori contaminated well water appears associated with the acquisition of a H. pylori infection. This study is based on a relatively small and inhomogeneous population sample and should be repeated to confirm the results.     

Auraptene attenuates gastritis via reduction of Helicobacter pylori colonization and pro-inflammatory mediator production in C57BL/6 mice

Helicobacter pylori is a major human pathogen that plays central roles in chronic gastritis and gastric cancer. Recently, we reported that auraptene suppressed H. pylori adhesion via expression of CD74, which has been identified as a new receptor for H. pylori urease. In this study, we attempted to clarify the effects of oral feeding of auraptene on H. pylori infection and resultant inflammatory responses in C57BL/6 mice and found that it remarkably attenuated H. pylori colonization and gastritis. Biochemical analyses revealed that auraptene inhibited H. pylori-induced expression and/or production of CD74, macrophage migration inhibitory factor, interleukin-1β, and tumor necrosis factor-α in gastric mucosa, together with serum macrophage inhibitory protein-2. It is notable that treatment with this coumarin during the pretreatment period was more effective than that during posttreatment. Our results suggest that auraptene is a promising phytochemical for reducing the risk of H. pylori-induced gastritis and carcinogenesis.