胃食管反流病患者食管功能与肥大细胞的研究进展

胃食管反流病（GERD）是胃内容物包括胃酸反流入食管、口咽或肺所引起的不适症状和（或）并发症的一种疾病,具有反复发作、难治愈的特点。目前关于GERD发病机制仍未完全阐明,尤其是非典型症状GERD的发病原因及相关机制。其中食管黏膜免疫炎症在GERD病理生理机制中的重要作用一直是研究者关注的重点。肥大细胞作为一种常见的免疫细胞,在人体消化道中广泛存在,通过细胞增殖、浸润、活化脱颗粒,释放介质等生物学活动,可对胃肠道发挥短期或长期的影响,在GERD、肠易激综合征、炎症性肠病等的发生发展中发挥重要作用。本文综述了GERD的相关发病机制,更好地提高临床医师对GERD及其并发症的认识,探索GERD治疗新靶点。     

缺氧与胃食管反流病关系的研究进展

胃食管反流病(GERD)的发生与胃酸反流相关,但确切的发病机制尚不明确,多数研究认为其是一种多因素相关性疾病。重度GERD与呼吸系统疾病(如气管炎性反应、哮喘等)的发生密切相关,而缺氧是大多数肺部疾病的病理生理改变之一。此文就缺氧本身对GERD发生发展的关系作一综述。     

2型糖尿病与胃食管反流病的相关性研究进展

2型糖尿病（T2DM）是目前发病率较高的代谢相关疾病,胃食管反流病（GERD）是发病率较高的消化道疾病之一,GERD被认为是T2DM并发症中慢性胃肠道疾病之一。T2DM和GERD的发生发展机制目前尚未研究明确,T2DM并发GERD患者影响食管动力学功能可能与胰岛素抵抗、高血糖、自主神经病变、胃肠激素、一过性下食管括约肌松弛及糖尿病药物使用有关,本文主要以T2DM与GERD相关性研究进展作以总结叙述。     

胃食管反流病的研究进展

<正>胃食管反流病(gastroesophageal reflux disease,GERD)是指胃内容物反流入食管引起的反流相关症状和(或)并发症的一种疾病。GERD在西方国家十分常见,近10年来中国人群的GERD患病率持续上升。现就2014年美国消化疾病学术会议周(digest disease week DDW)有关GERD的最新研究进展综述如下。1 GERD流行病学研究     

胃食管反流病与冠心病相关性的研究进展

随着临床上胃食管反流病（GERD）合并冠心病的患者逐年增加,两者之间相关性的研究越来越受到重视,部分消化系统疾病患者往往会出现类似心血管系统疾病的表现,给临床上对疾病的早发现、早诊断、早治疗带来了困扰。此文对GERD与冠心病之间联系的相关机制、造成疾病误诊的原因、相关危险因素等多个方面作一简要综述。     

胃食管反流病发病机制的研究进展

胃食管反流病(gastroesophageal reflux disease,GERD)是指胃内容物反流人食管引起不适症状和(或)并发症的一种疾病[1].迄今GERD的发病机制尚未完全阐明,有多种因素参与其中,本文就GERD发病机制的研究现状和进展作一介绍.     

胃食管反流病的诊断及治疗——胃食管反流病的病因与发病机理

胃食管反流病 (GERD)是指胃、十二指肠内容物反流入食管 ,引起烧心、胸痛、反酸等症状 ,导致食管炎及食管外组织损伤。 GERD是一种酸相关疾病 ,研究表明 ,GERD伴有酸反流 ,但常不伴有胃酸分泌增多 ,实际上是酸的错位。目前已认识到 ,GERD是多种因素促成的上消化道动力障碍性疾病 ,是抗反流防御机制下降和反流物对食管粘膜攻击力增强的结果 ,其中食管下括约肌 (L ES)功能失调起重要作用。现将GERD的主要病因及发病机理分述如下。1　 L ES压力低下或缺乏、L ES频发松弛患者的 L ES张力低下 ,当 L ES基础压力≤ 1.3k Pa(10 mm H…     

胃食管反流病的发病机制相关因素及其药物治疗

胃食管反流病（GERD）的蒙特利尔定义为胃内容物反流，引起令人烦恼的症状和（或）并发症。随着国人生活方式和饮食结构的改变，GERD已成为我国常见胃肠道疾病之一。GERD发病率、复发率高，长期严重影响患者生活质量，且诊治费用高。目前人们对GERD的认识仍不全面，本文就其发病机制相关因素和药物治疗作一简介。     

胃食管反流病的外科治疗

胃食管反流病(GERD)包括由病理性胃食管反流引起的反流性食管炎及并发症(食管狭窄、短食管、Barrett食管、哮喘、吸入性肺炎和反流性咽喉炎等)。GERD发病是多因素的，正常情况下，食管胃连接部存在抗反流屏障，可阻止胃内容物进笔食管。抗反流屏障损害、胃排空和食管酸廓清功能障碍是引发GERD的病理机制。     

胃食管反流病与胰岛素抵抗的研究进展

胃食管反流病（GERD）是胃、十二指肠内容物反流至食管内引起一系列症状及并发症的疾病。胰岛素抵抗是以高胰岛素水平为特征的葡萄糖调节障碍。有研究表明，GERD与胰岛素抵抗有关。胰岛素抵抗可能通过高血糖、肥胖等表现来引起胃食管反流病，而GERD，特别是糜烂性食管炎可通过炎症介质相关的机制来影响胰岛素敏感性从而引起胰岛素抵抗。本篇综述讨论关于胃食管反流病与胰岛素抵抗之间的相关性。     

Recent advances in the surgical treatment of achalasia and gastroesophageal reflux disease

Achalasia and gastroesophageal reflux disease (GERD) represent diverse physiologic disorders both of which result from lower esophageal sphincter (LES) dysfunction. Fortunately, both diseases are benign and amenable to surgically corrective therapies. Achalasia is characterized by destruction of the smooth muscle ganglion cells of the myenteric plexus (Auerbach) resulting in motor dysfunction, incomplete LES relaxation, and progressive esophageal dilation. GERD is frequently characterized by hypotonia or shortening of the LES. Local anatomical derangements such as a hiatal hernia (eg, sliding type I hernia) can predispose to GERD. Other predisposing factors for GERD include obesity, smoking, alcohol, and pregnancy. Transient LES relaxation is the most significant factor in the development of GERD. Transient LES relaxations last from 10 to 45 seconds and are not related to swallowing. The diagnostic workup of achalasia and GERD may include barium esophagram, upper gastrointestinal endoscopy, pH monitoring, and esophageal manometry. The different medical treatment options for achalasia comprise pharmacologic treatment, botulinum toxin, and balloon dilation. Surgical interventions include Heller myotomy, which is usually combined with a partial fundoplication. GERD is managed by treating the predisposing factors, using medications (ie, anatacids or proton pump inhibitors) and surgery (ie, fundoplication). Recently, endoluminal therapy has been employed in the treatment of GERD with promising short-term results.     

Enhanced expression of interleukin-8 and activation of nuclear factor kappa-B in endoscopy-negative gastroesophageal reflux disease

OBJECTIVE: Interleukin-8 (IL-8) mediates neutrophil trafficking via its receptors. Recent studies have shown that IL-8 is likely involved in the development and progression of erosive reflux esophagitis (RE), yet little is known about its implication in endoscopy-negative gastroesophageal reflux disease (GERD). The purpose of this study was to determine IL-8 messenger ribonucleic acid (mRNA) expression levels in endoscopy-negative GERD, along with assessment of nuclear factor kappaB (NF-kappaB) activation, which upregulates IL-8 expression. METHODS: We studied 31 patients with endoscopy-negative GERD, 15 patients with erosive RE, and 15 asymptomatic controls. Paired biopsy samples were taken from the esophagus 3 cm above the gastroesophageal junction; one biopsy was snap-frozen for measurement of IL-8 mRNA levels by real-time quantitative polymerase chain reaction, and another was formalin-fixed for histopathological evaluation. In nine endoscopy-negative GERD patients, the IL-8 mRNA expression levels were measured before and 8 wk after treatment with lansoprazole. We also sampled additional specimens for NF-kappaB-DNA binding assay and immunohistochemical analyses of NF-kappaB p65 and p50 subunits, IL-8 and specific IL-8 receptor, CXCR-1. RESULTS: The relative IL-8 mRNA expression levels were significantly higher in esophageal mucosa of patients with endoscopy-negative GERD than those of the controls. The presence of basal zone hyperplasia and intraepithelial neutrophils, histopathological hallmarks of GERD, were associated with higher levels of IL-8 mRNA. Lansoprazole treatment significantly reduced the IL-8 mRNA expression levels. The esophageal epithelium of patients with GERD showed intense immunoreactivity for IL-8, and expressed CXCR-1 antigen. We found NF-kappaB activation in esophageal mucosa in GERD patients and the NF-kappaB subunits were localized predominantly in the nuclei of IL-8-expressing cells. CONCLUSIONS: Our results demonstrate enhanced mucosal expression of IL-8 in incipient GERD even without mucosal breaks. NF-kappaB activation may be implicated in the pathogenesis in GERD.     

Epidemiological study on the incidence of gastroesophageal reflux disease symptoms in patients in acute treatment with NSAIDs

Gastroesophageal reflux disease (GERD) is one of the most common disorders in medical practice. The prevalence of GERD in Spain has been reported to be 15%. GERD is associated with esophageal and extra-esophageal complications and with a negative impact on the patients’ related quality of life. Several risk factors have been related with the development of GERD, including smoking, coffee intake, alcohol consumption and use of medication, such as NSAIDs. If untreated, GERD symptoms can lead to a decrease of patients’ related quality of life and to treatment discontinuation. From this study, it was confirmed that the relationship between GERD and some behavioral risk factors, such as alcohol intake, smoking and coffee consumption, and concomitant treatment with NSAID drugs. Among the protective factors for GERD, antisecretory agents and antacids have shown to be essential for the control of GERD, the use of proton pump inhibitors being the predominant protective factor.     

Interleukin-8 expression in the esophageal mucosa of patients with gastroesophageal reflux disease

BACKGROUND: It has been reported that inflammatory cell infiltration can be detected in patients with endoscopically negative gastroesophageal reflux disease (GERD) as well as those with erosive reflux esophagitis. In this study, we examined the expression of mRNA for interleukin (IL)-8, a potent chemokine for neutrophils, in the esophageal mucosa of patients with GERD and compared the results with their endoscopic findings and symptoms. METHODS: Biopsy samples were obtained from 80 patients. Endoscopic diagnosis was performed according to the Los Angeles classification. Patients with typical symptoms such as heartburn despite normal endoscopic findings were classified as the non-erosive GERD group. Total cellular RNA was extracted from the biopsy samples and IL-8 mRNA was quantified by real-time polymerase chain reaction (PCR). Localization of IL-8 protein in the esophageal mucosa was done by immunostaining. RESULTS: Expression of IL-8 mRNA was correlated with the endoscopic grade of esophagitis or with inflammatory cell infiltration, but not with the symptoms of the patients. Expression of IL-8 mRNA was also detected in all patients with non-erosive GERD. The level of IL-8 expression in non-erosive GERD was low compared with that in erosive GERD, but was higher than that in normal controls. IL-8 immunostaining was found in the basal layers of the esophageal mucosa. Administration of lansoprazole, a proton-pump inhibitor, decreased both IL-8 mRNA and protein levels in the esophageal mucosa. CONCLUSION: These results suggest that IL-8 in the esophageal mucosa may be involved in the pathogenesis of esophageal inflammation, including non-erosive GERD.     

Interleukin 8 and 1beta and RANTES levels in esophageal mucosa predict recurrence of endoscopy-negative gastroesophageal reflux disease

BACKGROUND/AIMS: Endoscopy-negative gastroesophageal reflux disease (ENRD), an incipient GERD phenotype without mucosal breaks, is a chronic relapsing condition with an impact on quality of life. Proinflammatory cytokines and chemokines play a role in the pathogenesis of various conditions including GERD. METHODOLOGY: This study investigated the relationship between interleukin 8 (IL-8), monocyte chemoattractant protein 1 (MCP-1), regulated on activation normal T-cell expressed and presumably secreted (RANTES) and IL-1beta levels in esophageal mucosa and recurrence of the reflux symptom in 22 patients with ENRD. RESULTS: Based on analysis using Cox's proportional hazard regression model, significantly positive association was observed between the mucosal levels of cytokines (IL-8 and -1beta and RANTES) and ENRD recurrence. Otherwise, parameters including age, gender, body mass index, smoking habits, alcohol intake, hiatal hernia and Helicobacter pylori status were not significantly related to relapse of the symptom. CONCLUSIONS: Enhanced production of such cytokines as IL-8 and -1beta and RANTES in esophageal mucosa can be potential predictors for ENRD recurrence.     

胃食管反流病患者食管外表现调查及危险因素分析

目的探究胃食管反流病（GERD）患者食管外表现发生情况及危险因素。 方法选取2012年4月至2017年12月,新疆维吾尔自治区人民医院诊断为GERD的200例患者的临床资料,通过单因素和多因素分析GERD患者食管外表现的发生率和危险因素。 结果患者出现食管外表现发生率为47.00%,其中反流性咽喉炎、反流性咳嗽和反流性哮喘分别为26.50%、15.55%、和12.00%,3者之间的发生无相关性;维吾尔族GERD食管外表现的发生率明显高于汉族（χ²=9.167 ,P=0.002 ）;多因素Logistic回归分析显示,维吾尔族、劳累、过饱食、饮食结构和GerdQ量表评分11~14及15~18是患者发生食管外表现的危险因素。 结论维吾尔族GERD患者的食管外表现发生率高于汉族,维吾尔族、劳累、过饱食、饮食结构和高GerdQ量表评分是GERD患者出现食管外表现的危险因素。     

Helicobacter pylori: a debated factor in gastroesophageal reflux disease

The prevalence of Helicobacter pylori infection is steadily decreasing in developing countries, and this has been paralleled by an increasing incidence of gastroesophageal reflux disease (GERD) and adenocarcinomas of the esophagus and of the esophagogastric junction. The prevalence of H. pylori infection, which is on the decline in Europe and in the United States, is probably related to improvements in sanitary conditions and socioeconomic status. These epidemiological data do not support a role for H. pylori in the pathogenesis of GERD, but at the same time suggest a negative association with the rising incidence in esophageal diseases. While H. pylori infection clearly does not cause GERD, it may protect certain susceptible individuals from the development of GERD and its complications. There are conflicting reports that GERD can develop after H. pylori eradication and that proton pump inhibitors are less effective in suppressing intragastric acidity in H. pylori negative patients--reasons not to eradicate H. pylori in GERD patients. On the contrary, other data suggest an increase in the development of atrophic gastritis in GERD patients (H. pylori positive) on long-term proton pump inhibitor therapy - a reason to eradicate H. pylori. Preexisting lower esophageal sphincter dysfunction, susceptibility to GERD, unmasking of latent GERD, and patterns and severity of gastritis may be important factors contributing to the development of GERD rather than just the presence or absence of infection with H. pylori.     

Effects of environment and lifestyle on gastroesophageal reflux disease

BACKGROUND: Gastroesophageal reflux disease (GERD) is comprised of a spectrum of related disorders, including hiatal hernia, reflux disease with its associated symptoms, erosive esophagitis, peptic stricture, Barrett's esophagus, and esophageal adenocarcinoma. Besides multiple pathophysiological associations among these disorders, they are also characterized by their comorbid occurrence in identical patients and by their similar epidemiologic behavior. The occurrence of GERD is shaped by marked temporal and geographic variations, suggesting the influence of environmental risk factors in the etiology of these diseases. VARIATIONS BY TIME, GEOGRAPHY, AND RACE: Between 1975 and 2005, the incidence of GERD and esophageal adenocarcinoma increased fivefold in most Western countries. The incidence of GERD also appears to be rising in the most developed countries of Asia. All severe forms of GERD, such as erosive esophagitis, peptic stricture, Barrett's metaplasia, and esophageal adenocarcinoma, are more common among whites than other ethnic groups. AFFLUENCE AND OBESITY AS RISK FACTORS: Barrett's esophagus and esophageal adenocarcinoma tend to occur slightly more often in subjects with higher income. Overweight and obesity contribute to the development of hiatal hernia, increase intra-abdominal pressure, and promote gastroesophageal reflux. Weight gain increases reflux symptoms, whereas weight loss decreases such symptoms. Other risk factors, such as smoking, alcohol, dietary fat, or drugs, play only a minor role in shaping the epidemiologic patterns of GERD. PROTECTION THROUGH HELICOBACTER PYLORI: On a population level, a high prevalence of H. pylori infection is likely to reduce levels of acid secretion and protect some carriers of the infection against reflux disease and its associated complications. Several studies have confirmed a lesser prevalence of H. pylori among subjects with than without GERD. Until recently, populations in Africa and Asia may have been protected against the development of GERD and esophageal adenocarcinoma by their higher prevalence of H. pylori infection. CONCLUSION: The study of environmental risk factors may provide an opportunity to better understand GERD and develop a means of its prevention.     

不同亚型胃食管反流病食管黏膜下层炎症因子变化特点研究

目的分析3种亚型胃食管反流病患者与对照组食管黏膜的组织变化和局部IL-4、IL- 6表达,探讨Th2型炎症因子在胃食管反流病发生发展中的作用。 方法选取2016年12月至2017年12月新疆维吾尔自治区人民医院69例患者临床资料,根据Gerd Q评分和内镜结果将所有入选研究者分为Barrett食管（BE）、糜烂性食管炎（EE）、非糜烂性反流病（NERD）和对照4组,利用食管24 h pH监测法评价胃食管反流病（GERD）患者食管酸暴露及反流特点;通过食管组织HE染色进行组织病理学评分,使用免疫组化法和酶联免疫吸附剂测定法检测食管局部及血清中IL-4、IL-6表达情况。 结果食管24 h pH监测结果中,3亚组间DeMeester指数、弱酸反流次数、反流总事件数比较,差异均无统计学意义（P均>0.05）,NERD组酸反流次数较其余2组低,差异有统计学意义（P均<0.05）;4组样本食管黏膜组织病理学评分中发现,BE组、EE组与其余2组相比均明显升高,差异有统计学意义（P均<0.05）,BE组与EE组评分之间亦有显著差异（P<0.05）,NERD组与对照组间差异不明显;IL-4在4组食管标本中均有不同程度表达,但4组间IL-4阳性率的比较并无显著差异（P均>0.05）;IL-6在NERD组和对照组表达量较低甚至不表达,EE组IL-6阳性率明显高于对照组（P<0.05 ）,但与NERD组间无显著差异,BE组阳性率与对照组和NERD组之间均有明显差异（P均<0.05 ）。 结论GERD食管黏膜上皮组织学炎症等级随食管炎的恶化而升高,其中NERD的食管组织学已出现炎性化趋势,但尚不足以与正常食管区别;IL-4在不同亚型GERD食管黏膜组织中的表达差异不及IL-6显著。