DIRECT CYTOPATHIC EFFECTS OF HELICOBACTER PYLORI ON HUMAN GASTRIC EPITHELIUM

幽门螺杆菌对人胃上皮的直接细胞病变作用

• 批准号: 5225849
• 负责人: DUANE T. SMOOT
• 金额: --
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/5225849
• 关键词: Helicobacter; cell adhesion; cellular pathology; clinical research; cytotoxicity; electron microscopy; gastric mucosa; gastrointestinal epithelium; genetic strain; host organism interaction; human subject; human tissue; lactate dehydrogenases; light microscopy; receptor binding; tissue /cell culture

Helicobacter pylori has been implicated as one of the most common causes of gastritis in man. This bacterium has been identified in 80-90% of adult patients with chronic gastritis and 90-100% of adult patients with peptic ulcer disease. Recent studies have shown that long-term infection by H. Pylori is associated with an increased risk of developing gastric carcinoma. However, the mechanism by which H. Pylori causes gastric epithelial cell injury is unknown and its role in the pathogenesis of peptic ulcer disease is even less understood. Infection with this bacterium is localized to the gastric mucosa, with the esophagus and duodenum only involved when heterotopic or metaplastic gastric epithelium is present in these areas. The prevalence of H. pylori infection of the gastric mucosa is very common in the United States. More than 50% of adults over 60 years of age are infected with this bacterium, and the prevalence in African Americans is approximately 38% higher than that of whites in all age groups. In this study, a human in vitro culture system is employed to identify the receptors to which H. Pylori binds on gastric epithelial cells is involved in its pathogenesis. Bacterial adherence, at least is part, may be responsible for H. pylori's predilection for gastric mucosa. Specific goals are to: (1) determine whether the differing pathology found in patients infected with this bacterium is secondary to the differences in toxin production between isolates or differences in host response to this bacterium; (2) identify the cytotoxin(s) produced by H. pylori; and (3) evaluate the mechanism of toxin induced cell injury on human gastric mucosa in vitro. Cell injury and viability is evaluated morphologically with light and electron microscopy and functionally by cell incorporation of neutral red dye and release of lactate dehydrogenase into culture media. Changes in epithelial cell proliferation associated with cell injury after exposure to this bacteria are being measured using bromodeoxyuridine. GCRC outpatient facilities will be useful in the acquisition of blood and other body secretions from clinical evaluations. GCRC inpatient facilities are not necessary for the early stages of this investigation, buy may become more critical as data are generated and subjects are in need of close monitoring and clinical evaluation.

幽门螺杆菌被认为是最常见的致病原因之一 人类的胃炎。这种细菌已经在80%-90%的 成人慢性胃炎患者和90%-100%的成人患者 消化性溃疡。最近的研究表明，长期感染 幽门螺杆菌感染与患胃病的风险增加有关 癌症。然而，幽门螺杆菌引起胃病的机制 上皮细胞损伤及其在糖尿病发病机制中的作用尚不清楚 消化性溃疡疾病更是知之甚少。感染了这种病毒 细菌定位于胃粘膜，包括食道和 十二指肠仅在异位或化生的胃上皮时受累 都出现在这些地区。儿童幽门螺杆菌感染的流行情况 胃粘膜在美国很常见。超过50%的 60岁以上的成年人感染这种细菌， 非洲裔美国人的患病率大约比美国人高38% 所有年龄段的白人。在本研究中，一种人体体外培养系统 被用来识别幽门螺杆菌在胃上结合的受体 上皮细胞参与了其发病机制。细菌黏附， 至少是部分原因，可能是幽门螺杆菌对 胃粘膜。具体目标是：(1)确定是否 在感染这种细菌的患者中发现的不同病理是 其次是不同菌株之间毒素产生的差异或 寄主对该细菌的反应差异；(2)鉴定 幽门螺杆菌产生的细胞毒素(S)；(3)评价其作用机制。 毒素对体外培养人胃粘膜的细胞损伤作用。细胞损伤 生命力是用光和电子从形态上进行评估的 显微镜下和功能上通过细胞掺入中性红染料和 将乳酸脱氢酶释放到培养基中。中的更改 暴露后上皮细胞增殖与细胞损伤的关系 用溴脱氧尿嘧啶核苷进行测定。GCRC 门诊设施将有助于获取血液和 临床评估的其他身体分泌物。GCRC住院患者 调查的早期阶段并不需要设施， 随着数据的生成和对象的加入，购买可能会变得更加关键 需要密切监测和临床评估。