胆汁反流致食管疾病的动物实验研究

近年来研究发现部分胃食管反流病及Barrett食管患者食管内除存在胃酸反流外，还存在胆汁反流。实验动物是研究胆汁反流致食管疾病的良好对象。食管灌注试验研究发现不同的十二指肠一胃反流成分致食管粘膜损伤的表现和损伤机制是不同的，与反流液的pH有关。食管胆汁反流动物模型研究提示存在反流性食管炎-Barrett食管一食管腺癌的发生模式，胆汁反流是病因之一，长期慢性炎症和氧化应激损伤是发病机制之一。胆汁反流致食管疾病的动物实验研究有助于对食管肿瘤的病因和发病机制的认识，为临床预防和治疗食管肿瘤提供新的思路。     

胆汁反流致食管疾病的动物实验研究

近年来研究发现部分胃食管反流病及Barrett食管患者食管内除存在胃酸反流外 ,还存在胆汁反流。实验动物是研究胆汁反流致食管疾病的良好对象。食管灌注试验研究发现不同的十二指肠 胃反流成分致食管粘膜损伤的表现和损伤机制是不同的 ,与反流液的pH有关。食管胆汁反流动物模型研究提示存在反流性食管炎 Barrett食管 食管腺癌的发生模式 ,胆汁反流是病因之一 ,长期慢性炎症和氧化应激损伤是发病机制之一。胆汁反流致食管疾病的动物实验研究有助于对食管肿瘤的病因和发病机制的认识 ,为临床预防和治疗食管肿瘤提供新的思路。     

胃食管反流病与胃酸胆汁联合反流的关系

目的探讨胃食管反流病(gastroesophagealrefluxdisease,GERD)与胃酸胆汁联合反流的关系。方法2002-09～2004-09河南大学淮河医院及新乡医学院第二附属医院住院及门诊GERD患者82例,其中非糜烂性反流病(nonerosiverefluxdisease,NERD)22例,反流性食管炎(refluxesophagitis,RE)31例,Barrett食管(Barrett esophagus,BE)29例及健康对照组20例。应用便携式24hpH监测仪和胆汁反流监测仪对三组患者及对照组进行24h食管内pH和胆汁动态联合监测。结果RE、BE患者胃酸和胆汁联合反流比NERD患者和对照组更加频繁。结论胃酸和胆汁的联合反流在RE和BE的发病机制中起着更加重要的作用,同步监测食管pH值及胆汁变化对RE、BE的诊断和治疗具有重要的意义。     

胃内胆汁反流相关因素的研究

胆汁和十二指肠其他内容物的反流和幽门螺杆菌 (Hp)感染等是上消化道黏膜炎症、溃疡乃至肿瘤的重要病因。胃部分切除术后 ,胃肠解剖结构的改变使十二指肠 胃反流危险增加 ,是残胃炎、残胃癌等的发病机制之一[1,2 ] 。然而 ,无手术史病人胃内胆汁反流的研究报道则较少 ,这些病人中胆汁反流与上消化道症状、Hp感染、胃内 pH值以及胃 食管反流病 (GERD)等的关系尚不尽明确。本研究通过胃内pH值和胆汁反流联合动态监测探讨无手术史病人的胃内胆汁反流与上消化道症状、GERD、胃内 pH值等的关系 ,以期加深对胃内胆汁反流的病理生理学机制的…     

胆汁反流性胃炎研究现状

胆汁反流性胃炎为临床常见病,发病率较高,其发病机制尚不明确且诊断较为困难,尚无"金标准"可寻。本文就近年来国内外关于胆汁反流性胃炎的发病机制、诊断、治疗作一概述。     

胆汁反流性胃炎胃动力及幽门螺杆菌感染情况的临床研究

目的研究原发性胆汁反流性胃炎的胃动力及幽门螺杆菌(H.pylori)感染情况,以探讨其发病机理。方法将原发性胆汁反流性胃炎118例作为试验组,慢性非萎缩性胃炎120例作为对照组,所有病例分别利用13C-辛酸呼气试验进行胃动力检查,利用13C-尿素呼气试验进行H.pylori检查,对比研究原发性胆汁反流性胃炎的胃动力及H.pylori感染情况。结果与慢性非萎缩性胃炎相比,原发性胆汁反流性胃炎的胃排空明显延迟(P0.05);原发性胆汁反流性胃炎H.pylori的阳性率为33.1%,慢性非萎缩性胃炎H.pylori的阳性率为55.8%,有统计学差异(P0.05)。结论原发性胆汁反流性胃炎存在胃动力障碍,反流的胆汁可能对幽门螺杆菌有抑制和杀灭作用。     

原发性胆汁反流性胃炎的研究进展

<正>胆汁反流性胃炎(bile reflux gastritis,BRG)是指过量的十二指肠液反流入胃引起的胃黏膜慢性炎症、糜烂甚至溃疡,胃部手术后发生的BRG称为继发性胆汁反流性胃炎,由非手术胃引起的BRG称为原发性胆汁反流性胃炎(primary bile reflux gastritis,PBRG)。目前,对前者研究较多,认识充分~([1]),对后者认识较少,发病情况尚不明确。本文对PBRG的发病机制及其诊断治疗做一综述。     

吸烟与胆汁反流的内镜观察

目的探讨吸烟与胆汁反流的相关性．方法对有消化道症状患者行内镜检查，并排除残胃患者共359例，检查前详细询问并记录是否吸烟、吸烟年限、平均日吸烟数量．仅以镜下见粘液湖黄绿染为胆汁反流标准研究．结果吸烟与不吸烟者胆汁反流的发生率有显著差异（P＜0．05），不吸烟者多于吸烟者；日均吸烟量及性别与胆汁反流的发生无显著相关性（P＞0．05，P＞0．01，P＞0．25）；吸烟年限与胆汁反流存在着高度显著性差异（P＜0．005），吸烟时间长胆汁及流发生率反而降低．结论吸烟、吸烟习惯及性别与胆汁反流的发生无关或关系不大，随着吸烟年限的延长，胆汁反流发生率下降的机制是否与影响神经、内分泌功能有关．     

胆汁反流性胃炎研究现状与展望

自从人类能够成功地开展胃手术以来，就有胆汁反流问题，但直到本世纪的60年代以后，人们才对胃内反流的胆汁进行较深入的研究【川．胆汁反流性胃炎由于过多的胆汁反流导致胃粘膜特殊的炎症性变化，引起一级以腹痛和胆汁性呕吐为特征的临床征候群，又称为胆汁反流性胃炎综合征（bilerefluxgAntritisslere），由于肠胃反流液呈碱性，又称碱性反流性胃炎（alkalinerefluxpens），由于胆汁反流不仅引起胃炎，尚可引起胃溃疡、胃癌和反流性食管炎等多种疾病，因而又称为肠胃反流病（duedempricrefluxdiseases）．作为一大类独立的病因，研究其…     

胆汁反流性胃炎与幽门螺杆菌感染及十二指肠溃疡关系探讨

胆汁反流是多种消化系疾病的病因之一，它与幽门螺杆菌(Hp)感染及十二指肠溃疡的发病关系尚不清楚。本文旨在探讨胆汁反流与Hp感染及十二指肠溃疡的发病关系。     

胆汁酸在食管腺癌发病中作用的研究进展

Barrett食管(BE)是食管腺癌(EAC)的癌前病变。BE患者的胆汁反流往往较非BE胃食管反流病患者更常见且更为严重,反流的胆汁酸刺激食管上皮细胞产生活性氧簇、炎症因子,引起DNA损伤,进而影响细胞增殖与凋亡,参与BE的恶性转化。本文对胆汁酸在EAC发病中的作用以及相关EAC预防策略作一综述。     

Importance of bile reflux in Barrett's esophagus

Barrett's esophagus (BE) is an acquired condition in which the squamous epithelial lining of the lower esophagus is replaced by a columnar epithelium due to chronic gastroesophageal reflux. The role of acid and bile in the development of esophageal mucosal injury and the formation of BE is controversial. Acid and pepsin are unquestionably important in causing mucosal damage and BE formation in both animal models and humans. Animal studies suggest the potential for synergistic damage from conjugated bile acids and gastric acid, as well as from unconjugated bile acids and trypsin in more neutral pH settings. Evidence of the involvement of bile and its constituents in humans has been less conclusive; however, the advent of better technology to detect bile reflux is beginning to clarify the role of these constituents. Human studies show that the reflux of bile parallels acid reflux and increases with the severity of gastroesophageal reflux disease, being most marked in BE. However, recent ex vivo studies suggest that pulses of acid reflux may be more important than bile salts in the development of dysplasia or adenocarcinoma in Barrett's epithelium. Nevertheless, antireflux surgery and aggressive acid suppression with proton pump inhibitors will decrease both acid and bile refluxes, and eliminate the synergism between these two duodenogastric constituents.     

胆汁在胃食管反流病中的作用

随着24 h食管pH监测和胆汁监测技术的开展,胃、十二指肠液混合反流在胃食管反流病(GERD)的发生、发展中的作用已被逐步认识.胆汁反流在GERD发病过程中所扮演的角色,成为近年来人们研究的焦点之一.基础研究证明胆汁在不同酸碱环境、不同浓度对食管黏膜的损伤作用是不同的.不少临床试验对GERD进行研究发现,胆汁反流与症状和食管损伤严重度存在一定关系,但研究结果不尽一致,胆汁在GERD中的作用仍有争议.明确胆汁在GERD中的作用,有助于为预防此类疾病开辟新的道路.本文就有关胆汁反流在胃食管反流病中的作用的研究进展作一综述.     

Bile reflux into the esophagus. Bilitec 2000 measurements in normal subjects and in patients after Nissen fundoplication.

BACKGROUND: Bilitec 2000 is a new spectrophotometric system that can detect bilirubin within the esophagus. The aim of this study was to test this new system in vitro and in vivo with special attention to patients operated on laparoscopically for gastroesophageal reflux with Nissen fundoplication. METHODS: In vitro studies of gallbladder bile dilution curves at different pHs were performed with a combined pH and Bilitec probe and by investigation of the drift of the Bilitec system. In vivo studies were performed in 34 normal individuals and 12 patients operated on with a laparoscopic Nissen fundoplication. Intra/intervariations were evaluated in normal individuals. RESULTS: The Bilitec system was able to detect changes in absorbance value within the range 0.14-0.6. Absorbance values were about 30% lower in an acid environment. The percentage of the total time with bile reflux was a median (range) of 3.9 (0-49.6) in normal individuals, with an intravariation within the intervariation, and 8.7 (0-36.6) in patients after a Nissen fundoplication. These values did not differ significantly. Eighty-two per cent of the normal subjects had some degree of bile reflux, if an absorbance value > or = 0.14 was accepted as the threshold value for the presence of bile reflux. CONCLUSIONS: Bile reflux in normal individuals is frequent and not different from that in patients after a Nissen fundoplication. Surprisingly, the latter had bile reflux but no or minimal acid reflux. Factors other than bilirubin may interfere with the measurements.     

Biliopancreatic and pancreatobiliary refluxes in cases with and without pancreaticobiliary maljunction: diagnosis and clinical implications

The sphincter of Oddi is located at the distal end of the pancreatic and bile ducts and regulates the outflow of bile and pancreatic juice. A common channel can be so long that the junction of the pancreatic and bile ducts is located outside of the duodenal wall, as occurs in pancreaticobiliary maljunction; in such cases, the action of the sphincter does not functionally affect the junction. Thus, biliopancreatic and pancreatobiliary refluxes occur, resulting in various pathological conditions in the biliary tract and in the pancreas. Biliopancreatic reflux could be confirmed by operative or postoperative T tube cholangiography, computed tomography combined with drip infusion cholangiography, histological detection of gallbladder cancer cells in the main pancreatic duct, and reflux of bile on the cut surface of the pancreas. Pancreatobiliary reflux could be diagnosed on the basis of an elevated amylase level in the bile, secretin-stimulated dynamic magnetic resonance cholangiopancreatography, and pancreatography via the minor duodenal papilla. Recently, it has become obvious that these refluxes can occur in individuals without pancreaticobiliary maljunction. Biliopancreatic reflux is related to the occurrence of acute pancreatitis, and pancreatobiliary reflux might be related to biliary carcinogenesis even in some individuals without pancreaticobiliary maljunction. Since few systemic studies exists with respect to diagnostic imaging techniques and clinical relevance of these refluxes in individuals with a normal pancreaticobiliary junction, further prospective clinical studies including appropriate management should be performed.     

Bile acids as components of the duodenogastric refluxate: detection, relationship to bilirubin, mechanism of injury, and clinical relevance

Excessive reflux of bile into the stomach or esophagus has been associated with a variety of benign and malignant foregut disorders. The interaction of gastric acid with bile acids and the development of mucosal damage has been studied extensively in in vitro and in vivo animal models. These studies show that soluble bile acids can enter mucosal cells when in their non-ionized lipophilic form, accumulate there up to eight times the luminal concentration, and thus cause injuries to cell membranes and tight junctions. Entrance of mucosal cells and accumulation are pH-dependent and more pronounced at acidic pH ranges. The noxious effect of bile on intestinal mucosa is thus related not only to the concentration of luminal bile acids but also to the pH and the mucosal exposure time. Due to the lack of objective and accurate tests to quantitate reflux of bile acids in vivo over prolonged periods of time, the concept of bile reflux as a pathogenic factor in the clinical situation has been controversial. Recent studies indicate that intraluminal bilirubin can be used as a reliable marker of bile reflux into the stomach or esophagus. Combined 24-hour monitoring of intraluminal pH and bilirubin with the newly-developed Bilitec system, despite some system-inherent shortcomings, therefore has the potential to clarify the interactions between bile reflux, mucosal injury and gastroesophageal carcinogenesis.     

Bile reflux into the stomach and the esophagus for volunteers older than 40 years

BACKGROUND: An increased incidence of Barrett's esophagus in cases with combined acidic and bile reflux is reported. The volunteers serving as controls in those studies were significantly younger than the patients. The aim of this study was to analyze bile reflux patterns of healthy volunteers aged comparably to patients with Barrett's esophagus. SUBJECTS AND METHODS: 19 older (8 f, 11 m; median age 51 years) (OV) and 20 younger (10 f, 10 m; median age 25 years) (YV) healthy volunteers without history of gastrointestinal disease or medication underwent simultaneous 24-hour pH and bile monitoring (Bilitec). All subjects consumed a special diet that did not interfere with bile measurements. Indicators for bile reflux in the stomach and esophagus: bilirubin probe absorption >0.25 in total measuring period (TM), upright position (excluding postprandial periods) (UP) and supine period (SP). RESULTS: There were no differences between older and younger volunteers in pH monitoring. Comparing the periods of bilirubin exposure of the stomach, the median (lower and upper quartile) percentage of time was OV = 5.7% (1.0-15.0%) and YV = 3.5% (0.1-7.8%) respectively for TM (n.s.), OV = 3.1% (0.7-9.4%) and YV = 0.4% (0.0-7.1%) for UP (n.s.), and OV = 2.1% (0.2-16.7%) and YV = 5.9% (0.0-12.2%) respectively for SP (n.s.). In 10/19 older volunteers and in 18/20 younger volunteers, no reflux of bile into the esophagus was measured. However, 4 older volunteers presented bile reflux from 4.6 to 51% of the total measuring period in contrast to the younger group with a maximum of 1.3% of TM. CONCLUSION: No significant differences in bile reflux into the stomach were distinguishable between younger and older healthy volunteers, but older volunteers more frequently exhibited bile reflux into the esophagus.     

反流性食管炎的临床研究

目的　探讨酸及胆汁反流在胃食管反流病 (GERD)中的发生情况及二者在GERD发病中的作用。方法　对 5 2例有反流症状的患者行内镜检查及 2 4hpH值和胆汁反流检测。结果　 5 2例受检者中 ,42例测得明显反流 ,其中混合反流占 5 9 5 % (2 5 /4 2 ) ,单纯反流仅占 40 5 % (17/4 2 )。在单纯反流中 ,以单纯酸反流为主 ,占 76 4% (13 /17) ;在混合反流中 ,以酸反流为主 ,反流程度较重 ,胆汁反流程度较轻 ;反流性食管炎在混合反流中的比例显著大于单纯酸反流 (P <0 0 5 ) ,且混合反流中的食管炎显著重于单纯反流 (P <0 0 5 ) ;反流症状发生的频率及严重程度与酸反流指数呈线性相关。结论　GERD中以混合反流为主 ;在混合反流及单纯反流中均以酸反流为主。酸反流和胆汁反流存在正性协同作用。酸反流是引起反流症状的主要原因     

Measurements of bile salt reflux are influenced by the method of collecting gastric juice

Conventional gastric analysis by continuous aspiration and a marker technique that allows the stomach to retain its volume were compared with respect to the measured rates of gastric secretion and bile salt reflux in 10 fasting subjects. In marker technique studies, the stomach contained 35.7 +/- 3.3 ml (mean +/- SEM) and emptied at a rate of 4.1% +/- 0.4% per minute. Secretion rates of volume and acid were similar in studies using continuous aspiration and in marker technique studies. In contrast, the bile salt reflux rate was significantly higher when continuous aspiration was performed (0.89 +/- 0.11 vs. 0.38 +/- 0.06 mumol/min, p less than 0.01). Gastric bile salt concentrations were also higher (765 +/- 48 vs. 366 +/- 67 mumol/L, p less than 0.01). This may be due to changes in the gastroduodenal pressure gradient induced by evacuating the stomach. It is concluded that measurements of bile salt reflux are influenced by the method of collecting gastric juice.     

Oesophagitis and bile reflux gastritis—clinical and histological assessments

BACKGROUND AND AIMS: Little is known concerning the relationship between oesophagitis and bile reflux (chemical) gastritis despite the numerous studies on gastritis related to Helicobacter pylori. Given the importance of bile in the pathogenesis of both gastric and oesophageal disorders, we aimed at assessing the chemical gastritis score in patients with or without oesophagitis. METHODS: Chemical/bile reflux gastritis score and bile reflux index were assessed in gastric biopsies taken from patients with oesophagitis and gastric surgery (group 1, n=9), gastric surgery without oesophagitis (group 2, n= 11), and oesophagitis without gastric surgery (group 3, n= 10). Endoscopic oesophageal damage was also graded on a 0-5 scale. RESULTS: Group 1 had a median (interquartile range) chemical score of 6 (4-9) compared with 8 (6-10) in group 2, and 1 (0-2) in group 3 (p=0.001; Kruskal-Wallis test for multiple group comparisons). Both the reflux gastritis score and bile reflux index were lowest in patients with intact stomachs. However, the oesophageal scores were 2 (1-2) in group 1 compared with 3 (2-5) in group 3 (p=0.01). CONCLUSION: Patients with post-surgical stomachs have similar chemical and related scores regardless of the presence or absence of oesophagitis. Despite the higher chemical gastritis scores, patients with gastric surgery, exposed mainly to bile reflux, have milder oesophagitis than those with intact stomachs, exposed to both gastric acid and bile.