Modlin I M, Zucker K A, Zdon M J, Sussman J, Adrian T E
Department of Surgery, VA Medical Center, New Haven, Connecticut.
J Surg Res. 1988 Mar;44(3):205-15. doi: 10.1016/0022-4804(88)90049-2.
Mastomys is a rodent which has been reported to develop spontaneous antral endocrine tumors with acid hypersecretion and duodenal ulceration. This study documents the establishment of a breeding colony and the characterization of the tumors and their possible secretagogues. Parietal cell secretory characteristics were studied using isolated gastric glands (IGG) of both normal (n = 5) and tumor-bearing animals. Tumors (n = 6) and control gastric tissue samples were examined by light transmission microscopy and immunohistochemistry. Gastrin was measured by radioimmunoassay in both plasma and tissue. IGG were prepared by collagenase dispersion and acid sequestration assessed by [14C]AP accumulation. Secretory mechanisms of this species were identified by establishment of a histamine dose-response curve and use of 8-bromo-cAMP. Receptor and proton pump inhibitions were assessed using cimetidine (10(-5)M) and the H/K ATPase inhibitor omeprazole (10(-5]. Both reduced [14C]AP accumulation significantly (P less than 0.05). 8-Bromo-cAMP and histamine significantly stimulated [14C]AP accumulation (P less than 0.05). Although parietal cells were substantially increased in tumor animals as compared to controls, the physiological parameters of acid secretion appeared normal in both and were comparable to other species which have been studied. Tumors were Grimelius positive and contained diffuse electron-dense granules. Immunohistochemistry was negative for gastrin, bombesin, serotonin, neuron-specific enolase, calcitonin, and pancreatic polypeptide. Tumor histamine-like immunoreactivity was, however, positive. Normal stomach contained 1001 +/- 185 compared to less than 0.5 pmole/g gastrin in tumors. Plasma gastrin was normal in both groups (29 +/- 5) as compared to 26 +/- 8 pmole/liter. This study characterizes a spontaneous gastric endocrine tumor which is associated with apparent parietal cell hyperplasia and reports of increased acid secretion and duodenal ulceration. The observations are consistent with the elaboration by the tumor of a nongastrin acid-trophic secretagogue.
多乳鼠是一种啮齿动物，据报道会自发发生胃窦内分泌肿瘤，伴有胃酸分泌过多和十二指肠溃疡。本研究记录了一个繁殖群体的建立以及肿瘤的特征及其可能的促分泌素。使用正常动物（n = 5）和荷瘤动物的分离胃腺（IGG）研究壁细胞的分泌特征。通过光学显微镜和免疫组织化学检查肿瘤（n = 6）和对照胃组织样本。通过放射免疫测定法测量血浆和组织中的胃泌素。通过胶原酶分散制备IGG，并通过[14C]AP积累评估酸螯合。通过建立组胺剂量反应曲线和使用8-溴-cAMP来确定该物种的分泌机制。使用西咪替丁（10（-5）M）和H/K ATP酶抑制剂奥美拉唑（10（-5）评估受体和质子泵抑制作用。两者均显著降低[14C]AP积累（P小于0.05）。8-溴-cAMP和组胺显著刺激[14C]AP积累（P小于0.05）。尽管与对照相比，荷瘤动物的壁细胞显著增加，但两者的胃酸分泌生理参数似乎正常，并且与已研究的其他物种相当。肿瘤Grimelius染色阳性，含有弥漫性电子致密颗粒。免疫组织化学检测胃泌素、蛙皮素、血清素、神经元特异性烯醇化酶、降钙素和胰多肽均为阴性。然而，肿瘤组胺样免疫反应性为阳性。正常胃中胃泌素含量为1001 +/- 185，而肿瘤中小于0.5 pmole/g。两组血浆胃泌素均正常（29 +/- 5），而对照组为26 +/- 8 pmole/升。本研究描述了一种与明显的壁细胞增生相关的自发性胃内分泌肿瘤，并报告了胃酸分泌增加和十二指肠溃疡。这些观察结果与肿瘤分泌一种非胃泌素酸营养促分泌素一致。
