胃粘膜傷害の回復性 -ラットの主細胞傷害時における経日的変化-

抄録

Gastric mucosal injuries induced by toxic insults generally show recovery after the withdrawal of the causative agent. One such agent is fusarenon-X (FX), a type B trichothecene mycotoxin and a potent gastric chief cell toxin. There are only a few reports regarding the recovery process after injury to chief cells. Therefore, we proposed an FX-induced mucosal injury to determine chief cell recovery after injury. Crl:CD(SD) rats were treated with a single gavage dose of FX (1.5 mg/kg or 3.0 mg/kg) or vehicle, and the stomach was examined histopathologically for 31 days post- treatment including immunohistochemical staining for gastric and pancreatic differential markers. After 48 hours post-treatment, a single cell necrosis and a decreased number of chief cells was noted. However, the single cell necrosis and decreased number of chief cells began to recover after day 2 and day 10, respectively. Eosinophilic changes in chief cells, which was positive for trypsinogen, suggested incomplete pancreatic acinar differentiation, was observed after day 2 and disappeared at the end of study. Doublecortin and calcium/calmodulin-dependent kinase-like-1 positive gastric progenitor cells and Trefoil factor 2 -positive mucus neck cells were ectopically observed at the base of the gastric glands within 10 days and within 3 days post-treatment, respectively. Additionally, pancreatic acinar metaplasia, which was positive for both trypsinogen and amylase, was observed 5 days post-treatment in the higher dose group. All histopathological findings described above showed the complete or tendency of recovery 31 days post- treatment. In conclusion, FX-induced gastric mucosal damage composed of chief cells injuries followed by promoted ectopic reproduction of gastric progenitor cells and abnormal differentiation of chief cells during its recovery process.