Department of Surgery, Royal College of Surgeons, Connolly Hospital, Blanchardstown, Dublin, Ireland.
Surgery. 2012 Mar;151(3):382-90. doi: 10.1016/j.surg.2011.08.021. Epub 2011 Oct 22.
The contribution of gastric acid to the toxicity of alkaline duodenal refluxate on the esophageal mucosa is unclear. This study compared the effect of duodenal refluxate when acid was present, decreased by proton pump inhibitors (PPI), or absent.
We randomized 136 Sprague-Dawley rats into 4 groups: group 1 (n = 33) were controls; group 2 (n = 34) underwent esophagoduodenostomy promoting "combined reflux"; group 3 (n = 34) underwent esophagoduodenostomy and PPI treatment to decrease acid reflux; and group 4, the 'gastrectomy' group (n = 35) underwent esophagoduodenostomy and total gastrectomy to eliminate acid in the refluxate. Esophaguses were examined for inflammatory, Barrett's, and other histologic changes, and expression of proliferative markers Ki-67, proliferating cell nuclear antigen (PCNA), and epidermal growth factor receptor (EGFR).
In all reflux groups, the incidence of Barrett's mucosa was greater when acid was suppressed (group C, 62%; group D, 71%) than when not suppressed (group B, 27%; P = 0.004 and P < .001). Erosions were more frequent in the PPI and gastrectomy groups than in the combined reflux group. Edema (wet weight) and ulceration was more frequent in the gastrectomy than in the combined reflux group. Acute inflammatory changes were infrequent in the PPI group (8%) compared with the combined reflux (94%) or gastrectomy (100%) groups, but chronic inflammation persisted in 100% of the PPI group. EGFR levels were greater in the PPI compared with the combined reflux group (P = .04). Ki-67, PCNA, and combined marker scores were greater in the gastrectomy compared with the combined reflux group (P = .006, P = .14, and P < .001).
Gastric acid suppression in the presence of duodenal refluxate caused increased rates of inflammatory changes, intestinal metaplasia, and molecular proliferative activity. PPIs suppressed acute inflammatory changes only, whereas chronic inflammatory changes persisted.
胃酸对碱性十二指肠胃反流物对食管黏膜毒性的贡献尚不清楚。本研究比较了存在胃酸、质子泵抑制剂 (PPI) 降低胃酸和不存在胃酸时十二指肠反流物的作用。
我们将 136 只 Sprague-Dawley 大鼠随机分为 4 组：第 1 组（n = 33）为对照组；第 2 组（n = 34）行食管-十二指肠吻合术促进“联合反流”；第 3 组（n = 34）行食管-十二指肠吻合术并给予 PPI 治疗以减少胃酸反流；第 4 组，“胃切除术”组（n = 35）行食管-十二指肠吻合术和全胃切除术以消除反流物中的胃酸。检查食管的炎症、Barrett 黏膜和其他组织学变化，以及增殖标志物 Ki-67、增殖细胞核抗原（PCNA）和表皮生长因子受体（EGFR）的表达。
在所有反流组中，抑制胃酸时 Barrett 黏膜的发生率更高（C 组 62%；D 组 71%），而非抑制胃酸时（B 组 27%；P = 0.004 和 P <.001）。PPI 和胃切除术组的糜烂发生率高于联合反流组。胃切除术组的水肿（湿重）和溃疡发生率高于联合反流组。PPI 组的急性炎症变化较联合反流组（94%）或胃切除术组（100%）少见，但 100%的 PPI 组存在慢性炎症。与联合反流组相比，PPI 组的 EGFR 水平更高（P =.04）。胃切除术组的 Ki-67、PCNA 和联合标志物评分均高于联合反流组（P =.006、P =.14 和 P <.001）。
十二指肠反流物存在时胃酸抑制导致炎症变化、肠化生和分子增殖活性增加的发生率增加。PPI 仅抑制急性炎症变化，而慢性炎症变化持续存在。
