Martinsen Tom C, Skogaker Nan E T, Bendheim Marianne Ø, Waldum Helge L
Institute of Intra-abdominal Diseases, Faculty of Medicine, Norwegian University of Science and Technology, MTFS, 7489 Trondheim, Norway.
Med Electron Microsc. 2003 Mar;36(1):18-32. doi: 10.1007/s007950300003.
Gastrin-producing G cells constitute one of the major populations of neuroendocrine cells in the antral mucosa of the stomach. The peroxisome proliferator-activated receptor (PPAR) alpha-agonist ciprofibrate is used as a lipid-lowering drug. Recently, ciprofibrate has been shown to induce hypergastrinemia in rats without reducing gastric acidity, which indicates a direct stimulatory effect on the G cell. Gastrin probably plays an important role in gastric tumorgenesis, and long-term dosing with ciprofibrate results in enterochromaffin-like (ECL) cell carcinoids in the oxyntic mucosa of rats. In this study, we aimed to examine changes of neuroendocrine granules in G cells following ciprofibrate dosing and relate them to changes induced by the proton pump inhibitor pantoprazole. Furthermore, we wanted to study peroxisomes in G cells. Rats received ciprofibrate 80 mg/kg/day or pantoprazole 200 mg/kg/day in 4 weeks. Antral mucosal specimens were processed for conventional staining procedures and immunocytochemistry for both the light and electron micro-scope. Specimens were immunolabeled for gastrin and peroxisome-specific proteins. Electron micrographs were analyzed planimetrically. This study shows that hypergastrinemia induced by ciprofibrate is accompanied by a decrease in granule number per cell and a relative increase in electron-dense granules. These changes were quite similar to those induced by pantoprazole, indicating signs of G-cell activation in general. However, distinctions concerning granule size and composition and both hypertrophy and hyperplasia of G cells are presented. Finally, demonstration of peroxisomes in G cells was only achieved by using the highly sensitive tyramide signal amplification technique in immunostaining for the peroxisome-specific protein PMP-70. Therefore, neither morphological nor quantitative changes of peroxisomes in G cells were detected.
产生胃泌素的G细胞是胃窦黏膜中主要的神经内分泌细胞群体之一。过氧化物酶体增殖物激活受体（PPAR）α激动剂环丙贝特用作降血脂药物。最近研究表明，环丙贝特可在不降低胃酸的情况下诱导大鼠出现高胃泌素血症，这表明其对G细胞有直接刺激作用。胃泌素可能在胃癌发生中起重要作用，长期给予环丙贝特会导致大鼠胃体黏膜中肠嗜铬样（ECL）细胞类癌。在本研究中，我们旨在检查给予环丙贝特后G细胞中神经内分泌颗粒的变化，并将其与质子泵抑制剂泮托拉唑诱导的变化相关联。此外，我们还想研究G细胞中的过氧化物酶体。大鼠在4周内接受80mg/kg/天的环丙贝特或200mg/kg/天的泮托拉唑。对胃窦黏膜标本进行常规染色程序以及用于光学和电子显微镜的免疫细胞化学处理。标本用胃泌素和过氧化物酶体特异性蛋白进行免疫标记。对电子显微镜照片进行平面测量分析。本研究表明，环丙贝特诱导的高胃泌素血症伴随着每个细胞颗粒数量的减少和电子致密颗粒的相对增加。这些变化与泮托拉唑诱导的变化非常相似，总体上表明G细胞激活的迹象。然而，在颗粒大小和组成以及G细胞的肥大和增生方面存在差异。最后，仅通过在过氧化物酶体特异性蛋白PMP-70的免疫染色中使用高灵敏度的酪胺信号放大技术才实现了G细胞中过氧化物酶体的显示。因此，未检测到G细胞中过氧化物酶体的形态或数量变化。
