胆汁反流对大鼠食管粘膜炎症损伤和凋亡的作用

目的 观察胆汁反流引起食管粘膜的炎症损伤和组织细胞凋亡情况。方法 以手术制造的十二指肠胃食管混合反流（DGER）大鼠模型为基础，制备DGER（A组）模型；DGER＋Losec Mupus制剂灌注造成单纯十二指肠液食管反流（B组）模型；DGER十胆管接扎造成无胆汁的十二指肠胃食管反流（C组）模型。观察9周后各组大鼠食管病理学改变，TUNEL法观察食管粘膜凋亡指数，免疫组化观察Fas蛋白的表达。结果 A、B、C三组均发生反流性食管炎表现，炎症以A组最重，其次为B组，C组最轻。A、B两组均见Barrett’s食管发生，发生率差异无统计学意义（P〉0．05），C组无Barrett’s食管发生；细胞凋亡结果示A组凋亡指数最高，其后依次为B组和C组（P〈0．01）；各组Fas蛋白表达均阴性。结论 不含胆汁的DGER所致食管损伤最轻，胆酸可能与Barrett’s食管的发生密切相关；各病理组的凋亡情况均增加，但与Fas系统无关。

Reflux of Bile Induces Esophageal Mucosal Inflammation and Apoptosis in Rats

OBJECTIVE: To investigate the esophageal mucosal inflammation and apoptosis induced by reflux of different duodenal or bile in rats. METHODS: Esophagus division in esophagogastric junction and then esophagoduodenostomy were performed on rats to make the models of duodenogastroesophageal reflux (DGER). Three kinds of reflux model, DGER (Group A), duodenoesophageal reflux without gastric juice (Group B) and DGER without bile (Group C) were made by adjusting the DGER models. 9 weeks after operation, the esophageal mucosal inflammation was examined under microscope, and the esophageal apoptosis was tested by DNA fragmentation in situ using TdT-mediated dUTP biotin nick end labling (TUNEL). Immunohistochemical method was used to detect the status of esophageal Fas protein (CD95) associated apoptosis. RESULTS: Evidences of reflux esophagitis were seen in all rats with different reflux models. Esophageal inflammation was most severe in group A, then in group B, and the slightest in group C. Barrett's esophagus was seen in group A and group B but not in group C, and the incidence was found to be of no difference between the A and B groups (P > 0.05). Esophageal mucosal apoptosis index in group A was (7.05 +/- 1.44)%, being significantly higher than that in group B (5.25 +/- 1.78)% and group C (2.84 +/- 1.36)%, (P < 0.01). The apoptosis index was significantly higher in group B than in group C (P < 0.01). Fas protein was negative in normal tissues and in all injured esophageal mucosal tissues. CONCLUSION: The DGER without bile inflicts the slighest injury on the esophageal mucosa. Bile may play a significant role in the induction of Barrett's esophagus. The apoptosis indices increase in groups A, B and C, but apoptosis is not correlated with Fas expression.