乳酸杆菌与胃内微生态

胃内微生态平衡对人体健康非常重要,一旦失衡使幽门螺杆菌过度繁殖,乳酸杆菌等正常菌群减少,就会导致许多疾病的发生。经研究发现乳酸杆菌对幽门螺杆茵具有明显的拮抗作用,乳酸杆菌通过微生态调节作用对幽门螺杆菌感染有预防和治疗的作用。     

乳酸杆菌与胃内微生态

胃内微生态平衡对人体健康非常重要，一旦失衡使幽门螺杆菌过度繁殖，乳酸杆菌等正常菌群减少，就会导致许多疾病的发生。经研究发现乳酸杆菌对幽门螺杆菌具有明显的拮抗作用，乳酸杆菌通过微生态调节作用对幽门螺杆菌感染有预防和治疗的作用。     

微生态制剂在溃疡性结肠炎治疗中的应用

微生态制剂定义为可促进肠道菌群平衡的微生物和物质。近年肠道菌群在溃疡性结肠炎（UC）发病中的作用日益受到关注,研究显示微生态制剂在UC诱导和维持缓解以及预防复发和并发症的发生中均有一定疗效,且不良反应较传统治疗少,因此有望成为治疗UC的新策略。本文就近年微生态制剂在UC治疗中的应用作一综述。     

人嗜酸乳杆菌对幽门螺杆菌的体外拮抗作用

幽门螺杆菌(Helicobacter pylori,Hp)是慢性胃炎[1-3]和消化性溃疡[4,5]的病原菌,与胃癌密切相关[6-9],WHO已将其列为Ⅰ类致癌因子[10-13].幽门螺杆菌在人群中的感染率高达50%以上[11],目前,临床主要采用含抗生素的三联药物(铋剂或质子泵抑制剂+甲硝唑+抗生素)治疗Hp感染[14],但不少患者出现严重副作用,顺从性差;多重抗菌药物会扰乱胃肠道内微生态平衡;尤其是抗生素疗法容易产生耐药性[15-17],在发展中国家,80%～90%Hp临床分离株对甲硝唑具有耐药性,在欧洲耐药菌株也高达25.6%,导致三联药物疗效降低,甚至失效,感染复发率高[18,19]率.微生态疗法,应用具有拮抗病原菌活性的活菌制剂治疗细菌感染[20],作用特异、直接、长久,无明显毒副作用,微生态制剂通过多种途径拮抗病原菌,减少了耐药性的发生,因此,微生态疗法为控制细菌感染性疾病提供了新的途径.1997年,Isogal et al研究发现,人胃和小鼠胃内存在乳杆菌、链球菌等正常菌群,Hp感染与乳杆菌数量有明显关系[21];Kabir et al发现:动物模型中乳杆菌能阻止Hp感染[22].     

幽门螺杆菌长期感染蒙古沙土鼠建立胃癌模型的研究

目的：幽门螺杆菌（Hp）长期感染蒙古沙土鼠（MGs)发生胃癌鲜见报道。本实验旨在研究Hp长期定植于MGs导致胃黏膜病变及其致癌性。方法：36只交封闭MGs（雌雄各半）分别接种Hp标准株ATCC43504，或从胃癌患者胃内分离的Hp161株，10只MGs作为对照，接种后第8、20、28和84周分别处死，检查细菌定植及胃黏膜病变情况。结果：绝大多数MGs胃内Hp持续定植，胃黏膜炎症随时间逐渐加重，第84周组织学特征是胃黏膜中－重度胃炎，以淋巴细胞为主的单核细胞弥漫性浸润，黏膜，黏膜下，甚至浆膜下有大量淋巴滤泡浸润，偶见淋巴上皮病变，萎缩，肠化较少见，上皮增生明显，24％（4／17）发生增生性息肉，第84周时18％（3／17）发生高分化腺癌（Hp161组1例，ATCC43504组2例；1雄2雌），结论：单独感染Hp能诱导MGs发生胃癌，并提示可利用不同种属的MGs和不同Hp菌株进行相关研究，首次报道了雌性MGs感染也可发生胃癌。     

胃肠道微生态与幽门螺杆菌根除治疗的相关性

胃肠道微生态系统庞大而复杂,影响因素众多,其中幽门螺杆菌(Hp)作为外源性细菌,可与胃肠道微生态产生相互影响。研究发现Hp感染可致肠道内嗜酸乳杆菌数量增多,胃内放线菌门、拟杆菌门和厚壁菌门数量减少。Hp根除治疗方案中的质子泵抑制剂和抗菌药物亦可影响胃肠道微生态。同时,胃肠道微生态可影响Hp在胃黏膜的定植,在根除Hp时联合使用益生菌可有效提高根除率,减少不良反应。     

胃内微生态与胃癌关系的研究进展

胃癌是世界第四大高发肿瘤,预后较差。胃癌的危险因素包括幽门螺杆菌(H.pylori)感染、吸烟、不良饮食习惯等,其中H.pylori感染是胃癌的独立危险因素。二代DNA测序技术揭示了复杂且与人类健康息息相关的胃肠道微生态系统。胃内共生菌之间的相互作用及其与胃部疾病的关系引起了临床医师的共同关注;阐明胃内菌群在H.pylori感染中的作用及其与胃癌的关系将为胃癌的诊断和治疗提供新的思路和希望。本文就胃内微生态与胃癌关系作一概述。     

胃癌及癌前病变中幽门螺杆菌感染与Ezrin蛋白表达的关系

目的探讨细胞骨架蛋白Ezrin在胃癌、癌前病变中的表达与Hp感染关系,及其在胃癌发生发展中可能的机制。方法采用免疫组化方法检测49例胃癌及癌前病变组织及16例正常胃黏膜标本中Ezrin蛋白的表达情况,并用快速尿素酶试验或Warthin．Starry胃螺旋染色法检测幽门螺杆菌（Hp）感染。结果胃癌及癌前病变组织Hp感染率显著高于正常组织（P〈0．01）;Ezrin蛋白表达在正常胃组织、癌前病变组织和胃癌组织中呈递减趋势,三者比较差异有统计学意义（P均〈0．05）;胃癌组织及癌前病变组织中Hp感染阳性组Ezrin蛋白的表达显著低于阴性组（P〈0．05）。结论在胃黏膜癌变过程中,Ezrin蛋白表达逐渐下调,Ezrin蛋白表达与Hp感染相关,提示Hp感染可通过影响Ezrin蛋白表达,在胃癌的发生发展过程中发挥一定作用。     

慢性肾功能衰竭患者肠道微生态变化及微生态制剂疗效观察

目的 :探讨慢性肾功能衰竭 (CRF)患者肠道微生态的变化及其与肾功能的关系 ,观察微生态制剂 (回春生 )治疗CRF的可行性。方法 :对CRF患者主要肠道菌群 (肠杆菌、肠球菌等需氧菌 ,双歧杆菌、类杆菌、乳杆菌等厌氧菌 )行定量培养 ,并检测肾功能 ;比较治疗前后肠道菌群、临床表现以及肾功能的变化。结果 :CRF患者普遍存在肠道微生态平衡的紊乱 ,主要体现在需氧菌群过度增殖 ,厌氧菌群明显受抑 ,且与肾功能状况明显相关 ;微生态制剂有助于改善此种失衡 ,促进临床表现与肾功能的改善。结论 :肠道微生态失衡参与了CRF的发展、恶化过程 ,微生态制剂可能为CRF的治疗提供一条新的途径。     

幽门螺杆菌毒力因子及其诱发胃癌作用机制研究进展

幽门螺杆菌（Hp）属于革兰阴性菌,可以在人胃内存活并定植。Hp能够利用其毒力因子调节宿主炎症反应,破坏胃黏膜,其感染的长期结局包括胃癌和胃黏膜相关淋巴组织淋巴瘤等恶性肿瘤,是与胃癌相关的Ⅰ类致癌物。与Hp生存相关的毒力因子主要是脲酶,在脲酶的帮助下,Hp可以在pH值极低的胃内生存,形成持久感染;与Hp定植相关的毒力因子包括外部炎症蛋白A、Hp外膜蛋白Q、血型抗原结合黏附素,这些毒力因子与宿主胃上皮细胞相互作用,帮助Hp在胃黏膜定植,增加癌前病变及胃癌发生风险;与Hp致病相关的毒力因子包括细胞毒素相关基因A、空泡细胞毒素、外膜囊泡、γ-谷氨酰转肽酶、高温需求蛋白A等,Hp在胃上皮细胞存活、黏附并成功定植后,上述毒力因子进一步诱导炎症反应,促进细胞增殖、侵袭和转移,促使胃部炎症向胃癌转化。深入研究Hp毒力因子诱导胃癌发生的机制,有助于为胃癌的诊断和治疗提供新思路和方法。     

浅表性胃炎、胃粘膜不典型增生及胃癌组织中COX-1、COX-2、iNOS表达的意义

目的：研究ＣＯＸ－１、ＣＯＸ－２、ｉＮＯＳ于浅表性胃炎、胃粘膜不典型增生及胃癌中表达的意义,探讨ＣＯＸ－２,ｉＮＯＳ与胃癌、幽门螺杆菌（Ｈｐ）感染的关系。方法应用多克隆抗体ＣＯＸ－１,ＣＯＸ－２、ｉＮＯＳ免疫组化方法检测３３例浅表性胃炎、３０例胃粘膜不典型增生、２９胃癌石蜡包埋组织中的ＣＯＸ－１、ＣＯＸ－２、ｉＮＯＳ表达情况及Ｈｐ感染率。结果ＣＯ２－２,ｉＮＯＳ在胃癌中的表达率明显高于浅表性胃炎（     

Mechanism for gastric cancer development by Helicobacter pylori infection

Helicobacter pylori (H. pylori) infection plays a crucial role in the development of gastric cancer. There are two major pathways for the development of gastric cancer by H. pylori infection: the indirect action of H. pylori on gastric epithelial cells through inflammation, and the direct action of the bacteria on epithelial cells through the induction of protein modulation and gene mutation. Both pathways work together to promote gastric carcinogenesis.     

筛查幽门螺杆菌感染预防胃癌的费用效果分析

目的评价在人群中筛选幽门螺杆菌感染以预防胃癌的临床和经济学效果.方法用Markov模型估计在10万名40岁～45岁人群中筛查幽门螺杆菌感染者并对筛查试验阳性者进行治疗的远期效果及费用,并与不进行任何干预的结果相比较,进行卫生经济学评价.对治疗感染者减少胃癌发生危险度的有效率和胃癌发病率进行敏感性分析.结果在有效率为50%时,每筛查10万人可减少291例胃癌的发生,增加2612个生命年.当预防胃癌的有效率从5%到100%变化时,每增加一个生命年的费用从7747元下降到2325元,在胃癌高发区筛查更经济有效.结论筛查幽门螺杆菌感染是一种潜在的能减少胃癌发生的有效措施.     

Association of cyclooxygenase-2 expression with Hp-cagA infection in gastric cancer

AIM: To observe the expression of cyclooxygenase-2 (COX-2) and to investigate the association between COX-2 expression and infection with cytotoxic-associated gene A (cagA) positive strain Helicobacter pylori (Hp) in human gastric cancer, and subsequently to provide fresh ideas for the early prevention of gastric cancer. METHODS: 32 Specimens of gastric cancer and corresponding adjacent normal gastric mucosa were obtained from patients who had undergone surgical operations of gastric cancer. All the samples including 1 case of stomach malignant lymphoma and 31 cases of gastric adenocarcinoma were confirmed by pathology diagnosis. The expression of COX-2 in 32 specimens of gastric cancer and corresponding adjacent normal gastric mucosa was quantitatively determined and analyzed with Flow Cytometry, and the levels of COX-2 protein were compared between specimens with cagA(+) Hp infection and those without cagA(+) Hp infection. The cagA gene in 32 specimens of gastric cancer was detected by polymerase chain reaction (PCR) method. RESULTS: Twenty-seven of 32 (84 %) specimens of gastric cancer showed over-expression of COX-2, compared with the adjacent normal gastric mucosa. cagA(+) gene were detected from 19 specimens of gastric cancer, but not from the other 13 specimens. The levels of COX-2 protein in 19 specimens of gastric cancer with cagA(+) Hp infection (the number of positive cells was 73.82+/-18.2) were significantly higher than those in the 13 specimens without cagA(+) Hp infection (the number of positive cells was 35.92+/-22.1). CONCLUSION: COX-2 is overexpressed in gastric cancer and cagA(+) Hp infection could up-regulate the expression of COX-2 in gastric cancer in human. There may also exist another way or channel to regulate the expression of COX-2 in gastric cancer in addition to cagA(+) Hp infection. Therefore, applying COX-2 selective inhibitors could be an effective and promising way to prevent gastric cancer.     

胃癌和癌前病变中幽门螺杆菌及环氧化酶-2和p53的表达及相关性研究

[目的]检测慢性胃炎、胃癌前病变及胃癌（GGa）的胃黏膜组织中幽门螺杆菌（Hp）,环氧化酶-2（COX-2）和突变型p53的表达,探讨Hp感染在胃癌发生过程中与COX-2、p53动态表达的相关性.[方法]选择经胃镜检查及病理组织学证实为慢性浅表性胃炎（CSG）、慢性萎缩性胃炎（CAG）、肠上皮化生（IM）、不典型增生（Dys）及GCa患者各100例,快速尿素酶试验（HPUT法）和组织学改良Giemsa染色联合检测Hp,通过免疫组化检测Hp感染组和非感染组患者胃黏膜COX-2、p53.[结果]①Hp、COX-2阳性率随病变进展呈上升趋势,Hp阳性率在CAG、IM、Dys、GCa各组中显著高于CSG组（P＜0.05）;COX-2在IM、Dys、GCa各组中与慢性胃炎比较有统计学意义（P＜0.05）;②Hp感染阳性率和COX-2蛋白表达阳性率在胃癌前病变组织中存在相关性（P＜0.05）;③p53阳性率在GCa与CSG、CAG相比差异有统计学意义（P＜0.01）;④在GCa组中,Hp阳性组p53的阳性表达明显高于Hp阴性组（P＜0.05）.[结论]GCa的形成与Hp感染、突变型p53、COX-2等多种因素及其相互作用有关,可视为GCa发生的危险预警信号之一;在GCa高危人群的追踪观察和随访中,进行Hp、p53、COX-2的联合检测,对发现胃癌前病变和GCa有一定临床意义.     

Prevalence of gastric cancer decreases with age in long-living elderly in Japan, possibly due to changes in Helicobacter pylori infection status

OBJECTIVES: The prevalence of Helicobacter pylori (Hp) infection and the development of gastric cancer are both believed to increase with age in Japan. However, no studies have investigated people older than 65 years in detail. In this study, we investigated the prevalence of Hp infection and gastric cancer in the elderly, and analyzed the influence of both factors on longevity. METHODS: All patients investigated were 65 years old and over. A total of 1877 autopsy cases were used to investigate the prevalence of gastric cancer and colonic cancer. Serum samples were obtained from 644 patients with dyspepsia and analyzed for Hp-IgG antibodies. Of these 644 patients, 63 underwent upper gastrointestinal endoscopies. Five biopsies were obtained and evaluated for the following morphological variables: neutrophils, mononuclear cell, atrophy, and intestinal metaplasia. Hp infection was evaluated histologically and with the (13)C-urea breath test. RESULTS: The prevalence of gastric cancer was significantly lower in subjects older than 85 years. The positive rate of serum Hp-IgG, and Hp infection as detected histologically and by the (13)C-urea breath test, also decreased with age. In Hp(+) patients, the neutrophil score significantly decreased with age. In Hp(-) patients, however, the intestinal metaplasia score significantly increased with age. CONCLUSIONS: The non-infection of Hp itself is not related to longevity in Japanese elderly, because even Hp(-) patients appear to have been infected previously with Hp. The lower prevalence of gastric cancer in the elderly may be due to the disappearance of Hp colonization, which may contribute to longevity in Japanese elderly.     

胃粘膜癌变过程中幽门螺杆菌感染与p53,c-erbB-2基因表达的研究

目的探讨胃粘膜癌变过程中幽门螺杆菌（Ｈｅｌｉｃｏｂａｃｔｅｒｐｙｌｏｒｉ,Ｈｐ）感染与ｐ５３,ｃｅｒｂＢ２基因表达的关系．方法浅表性胃炎１６例,肠上皮化生２２例,异型增生１４例,早期胃癌１８例及进展期胃癌４０例作为研究对象．用ＷａｒｔｈｉｎＳｔａｒｙ银染色法检测Ｈｐ,用免疫组化Ｓｐ法检测ｐ５３和ｃｅｒｂＢ２的基因表达产物．结果Ｈｐ,ｐ５３,ｃｅｒｂＢ２在浅表性胃炎的检出率各为５００％,００％,００％;在肠上皮化生的检出率各为５９１％,２２７％,１３６％;在异型增生的检出率各为８５７％,６４３％,２８６％;在早期胃癌的检出率各为１６７％,３３３％,１１１％;在进展期胃癌的检出率各为５０％,５２５％,５５０％;在癌旁粘膜的Ｈｐ检出率为８６７％;在癌前病变中,Ｈｐ阳性组的ｐ５３,ｃｅｒｂＢ２表达率均高于Ｈｐ阴性组．结论Ｈｐ感染参与了胃癌前病变的发生与发展;Ｈｐ感染可引起野生型ｐ５３基因失活和ｃｅｒｂＢ２基因激活,从而导致胃粘膜的癌变．     

胃癌癌旁组织中幽门螺杆菌感染及基因改变

应用ＰＣＲ、ＰＣＲ／ＲＦＬＰ对胃癌及癌旁组织中Ｈｐ感染进行了检测，并应用ＰＣＲ／ＲＦＬＰ、ＰＣＲ／ＳＳＣＰ、ＰＣＲ－ＤＮＡ测序探讨了Ｈｐ感染与ｒａｓ基因、ｐ５３基因变化的关系。研究结果发现：２４例胃癌组织Ｈｐ阳性１２例（１２／２４，５０％），２４例癌旁组织Ｈｐ阳性１１例（１１／２４，４８．５％），两者无显著差异，胃癌组基因改变者１７例（１７／２４，７０．８３％），其中Ｈｐ阳性１２例（１２／１７，７０．５９％），７例无基因改变者未发现Ｈｐ感染。癌旁组基因改变者１例，其中Ｈｐ为阴性。２４对胃癌ｐ５３Ｅｘｏｎ４的杂合缺失率为４７．３７％（９／１９）。ｐ５３Ｅｘｏｎ５、６、７、８突变在癌组织中有１１例（１１／２４；４５．８％），癌旁组仅一例，发生Ｈ－ｒａｓ１２位点突变者７例（７／２４，２９．１７％），癌旁组则无突变。胃癌基因改变与Ｈｐ＋相关性比较发现，Ｈｐ感染与基因改变关系密切（Ｐ＜０．０１）。各种基因改变中以ｐ５３改变似与Ｈｐ感染关系更紧密（ｒ＝０．５Ｐ＜０．０５）。结果表明，ｒａｓ基因及ｐ５３基因的协同作用在胃癌的致病机理中显示出重要作用。在癌变过程中，可能Ｈｐ的感染是基因改变进而促进组织恶变的促动因素之一。     

Treatment of Helicobacter pylori and prevention of gastric cancer

Gastric cancer is the second commonest fatal malignancy in the world with a high incidence in China. Helicobacter pylori infection is an important factor in the pathogenesis of gastric cancer. Epidemiological studies have shown a strong causal relationship between H. pylori infection and gastric cancer. Animal studies also show that eradication of H. pylori infection, especially at the early stage, is effective in preventing H. pylori-related gastric carcinogenesis. H. pylori eradication leads to regression and prevents the progression of gastric precancerous lesions, but only in a minority of cases. H. pylori eradication appears to be the most promising approach in gastric cancer prevention. The current available data in human studies showed that H. pylori eradication can reduce the risk of developing gastric cancer and this strategy is more useful in patients without atrophic gastritis or intestinal metaplasia. A longer follow-up and additional studies are needed for better understanding this issue.     

Proton pump inhibitors (PPIs) may cause gastric cancer – clinical consequences

Recently, two epidemiological studies showed that long-term treatment with proton pump inhibitors (PPIs) increased the risk of gastric cancer. It is well known that hypergastrinemia predisposes to gastric neoplasia in animals as well as man. Recently a study showed that hypergastrinemic patients had an increased risk of gastric cancer when followed for about 25 years. It is likely that hypergastrinemia is the pathogenic factor for gastric carcinogenesis due to PPI. PPI are the only group of drugs that causes long-term hypergastrinemia in the doses used in a clinical setting. Due to the likely carcinogenic effect, PPIs should be used carefully. Moreover, since the carcinogenic effect of Helicobacter pylori (Hp) infection also may be mediated by an increase in gastrin, Hp should be eradicated whenever treatment with PPI is initiated. In peptic ulcer disease Hp eradication is the treatment of choice. Gastro-oesophageal reflux disease (GERD) is the most prevalent condition leading to long-term use of inhibitors of gastric acid secretion. Only in severe oesophagitis should the treatment be initiated by PPIs, whereas histamine-2 (H-2) blockers ought to be the initial option in most cases of GERD particularly since PPI treatment induces tolerance to H-2 blockers. In the cases where long-term PPI treatment is necessary, the dose should be adjusted by the determination of chromogranin A, which in a way reflects 24-h gastrin exposure. Finally, due to latency of neoplasia, the use of PPI must be very restricted in children and young adults.