Karam S M, Forte J G
Department of Molecular and Cell Biology, University of California, Berkeley 94720.
Am J Physiol. 1994 Apr;266(4 Pt 1):G745-58. doi: 10.1152/ajpgi.1994.266.4.G745.
Parietal cell morphology was studied after chronic inhibition of gastric H(+)-K(+)-adenosinetriphosphatase (ATPase) by omeprazole. Gastric mucosa from rabbits treated with omeprazole every 12 h (1 mg/kg sc) for 5 days were compared with sham-injected animals using immunohistochemistry and electron microscopy. Three immunocytochemical markers, including antibodies against the alpha- and beta-subunits of the H(+)-K(+)-ATPase, showed that some parietal cells in omeprazole-treated rabbits displayed light areas and granularity in their cytoplasm. These abnormalities were also apparent in semithin sections. Electron microscopy was used to categorize and quantitate the specific structural abnormalities in parietal cells. Cells were classified as normal, altered, or degenerated. For control tissues, altered and degenerated parietal cells were few; they collectively represented 6% of total parietal cells and were located mainly deep in the gland base. For omeprazole-treated tissues, altered and degenerated parietal cells occurred throughout the gland and averaged 62% of total parietal cells. In addition, macrophages invaded the mucosa presumably to eliminate degenerated cells. Although there was an increase in parietal cell degeneration, enhanced parietal cell generation was suggested by increases in mitosis among proliferative cells and, more specifically, in the number of preparietal cells. After 3 days of recovery from the omeprazole regimen, parietal cells and the gastric mucosa appeared to recover the normal morphology. In conclusion, blocking H(+)-K(+)-ATPase by omeprazole enhances degeneration and macrophage-mediated elimination of parietal cells and also causes an increase in preparietal cell production. Thus omeprazole temporarily changes the dynamic features of parietal cells in the rabbit to make them die early and grow fast.
采用奥美拉唑对胃H(+)-K(+)-三磷酸腺苷酶（ATP酶）进行慢性抑制后，对壁细胞形态进行了研究。将每12小时接受一次奥美拉唑（1mg/kg，皮下注射）治疗5天的家兔胃黏膜，与假注射动物的胃黏膜进行比较，采用免疫组织化学和电子显微镜技术。三种免疫细胞化学标志物，包括抗H(+)-K(+)-ATP酶α和β亚基的抗体，显示在接受奥美拉唑治疗的家兔中，一些壁细胞的细胞质出现浅色区域和颗粒状。这些异常在半薄切片中也很明显。利用电子显微镜对壁细胞的特定结构异常进行分类和定量。细胞被分为正常、改变或退化。对于对照组织，改变和退化的壁细胞很少；它们总共占壁细胞总数的6%，主要位于腺底部深处。对于接受奥美拉唑治疗的组织，改变和退化的壁细胞遍布整个腺体，平均占壁细胞总数的62%。此外，巨噬细胞侵入黏膜，可能是为了清除退化细胞。虽然壁细胞退化有所增加，但增殖细胞中的有丝分裂增加，更具体地说，前壁细胞数量增加，提示壁细胞生成增强。在从奥美拉唑治疗方案中恢复3天后，壁细胞和胃黏膜似乎恢复了正常形态。总之，奥美拉唑阻断H(+)-K(+)-ATP酶可增强壁细胞的退化和巨噬细胞介导的清除，还可导致前壁细胞生成增加。因此，奥美拉唑暂时改变了家兔壁细胞的动态特征，使其过早死亡并快速生长。
