儿童原发性十二指肠胃反流对胃黏膜损伤的作用

Pathogenic effects of primary duodenogastric reflux on gastric mucosa of children

目的观察儿童原发性十二指肠胃反流（DGR）对胃黏膜的损伤作用，并初步探讨DGR与临床症状、幽门螺杆菌感染和胃内酸度的关系。方法对81例因腹痛、饱胀、恶心、呕吐等上消化道症状就诊的患儿，进行临床症状评分、胃镜检查、胃窦黏膜组织病理学检查和24h胃内胆红素监测，其中51例同步行24h胃内pH监测。以胆汁反流总时间百分比作为胆汁反流程度的指标。根据胃窦黏膜的胃镜下改变以及组织病理学特征变化有无进行分组，分别比较2组的胆汁反流程度。并对胃内胆汁反流与临床症状评分、胃内酸度以及Hp感染等进行相关性分析。结果胃窦黏膜有充血者[17．1％（0．5％～53．2％）]较无充血者[6．5％（0～58．6％）]（Z=-1．980），有黄染者[19．8％（0．5％～58．6％）]较无黄染者[8．8％（0～38．0％）]（Z=-2．956），胆汁反流总时间百分比高，差异均有统计学意义（P〈0．05或0．01）；胃窦黏膜组织病理学检查，有肠化组胆汁反流总时间百分比[29．0％（1．9％～58．6％）]较无肠化组[14．3％（0～53．7％）]长，差异有统计学意义（Z=-2．026，P〈0．05）。有慢性炎症组与无慢性炎症组、有活动性组与无活动性组相比，胆汁反流程度差异无统计学意义（P〉0．05）。胆汁反流严重度与饱胀症状正相关（r=0．258，P〈0．05），与Hp感染（r=0．016）和胃内酸度（r=0．124）无明显相关性（P均〉0．05）。结论原发性DGR可致儿童胃窦黏膜损伤，胃镜下主要表现为胃窦黏膜充血和黄染，病理组织学变化上与肠上皮化生有关，与炎症细胞浸润无关。DGR与Hp感染和胃内酸度均无关，DGR可能是一个独立的致病因素，与Hp感染和胃酸一起共同对胃黏膜造成损伤。

Objective Duodenogastric reflux （DGR） is a reverse flow of duodenal juice into stomach through pylorus composed of bile acid, pancreatic secretion, and intestinal secretion. The increased entero-gastric reflux results in mucosal injury that may relate not only to reflux gastritis but also esophagitis, gastric ulcers, carcinoma of stomach and esophagus. However, the exact mechanisms of gastric mucosal damage caused by DGR are still unknown. The objective of the present study is to investigate the pathogenic effect of primary DGR on gastric mucosa in children, and to explore the correlation of DGR with clinical symptoms, Hp infection and intragastric acidity. Method Totally 81 patients with upper gastrointestinal manifestations were enrolled and they were graded according to the symptom scores and underwent endoscopic, histological examinations and 24-hour intra-gastric bilirubin was monitored with Bilitec 2000. Of the 81 cases, 51 underwent the 24-hour intra-gastric pH monitoring by ambulatory pH recorder simultaneously. The total fraction time of bile reflux was considered as a marker to evaluate the severity of DGR. The total fraction time of bile reflux was compared between the patients with positive and negative results under endoscopy and histologically, respectively. The correlations of the total fraction time of bile reflux with clinical symptom score, Hp infection, intragastric acidity were analyzed respectively. Result The total fraction time of bile reflux in the patients with hyperemia and yellow stain gastric antral mucosa under endoscopy was significantly higher than that without those changes [ 17. 1% （0. 5% ～ 53. 2% ） vs.6.5%（0～58.6%）, Z= - 1.980,P〈0.05;19.8% （0.5% ～58.6%）vs. 8.8%（0～38.0%）, Z= -2. 956, P 〈 0.01 respectively]. Histologically, the cases with intestinal metaplasia had significantly higher total fraction time of bile reflux than in the cases without intestinal metaplasia E 29. 0% （ 1.9% ～ 58.6% ） vs. 14. 3% （0 ～53.7% ）, Z = -2. 026, P 〈0. 05], but no significant difference was found either between the cases with and without chronic inflammation （ P 〉 0.05 ） or between the cases with and without active inflammation （ P 〉 0. 05 ）. The severity of bile reflux was positively correlated with the score of abdominal distention （ r = 0. 258, P 〈 0. 05 ）, but no correlation with either the severity of intragastric acid （r= -0. 124, P〉0.05）, or Hp infection （r=0.016, P〉0.05） was found. Conclusion Primary DGR could cause gastric mucosal lesions manifested mainly as hyperemia and bile-stained gastric antral mucosa under endoscopy and the gastric antral intestinal metaplasia histologically in children. There was no significant correlation between DGR and gastric mucosal inflammatory infiltration. DGR had no relevance to Hp infection and intragastric acidity. We conclude that DGR is probably an independent etiological factor and might play a synergistic role in the pathogenesis of gastric mucosal lesions along with gastric acid and Hp infection.