Impaired gastric acid secretion in gastrin-deficient mice
Impaired gastric acid secretion in gastrin-deficient mice
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DOI：
10.1152/ajpgi.1998.274.3.g561
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发表时间：
1998-03-01
影响因子：
4.5
通讯作者：
Samuelson, LC
中科院分区：
文献类型：
--
作者：
Friis-Hansen, L;Sundler, F;Samuelson, LC
为了进一步了解肽激素胃泌素在胃的发育和功能中的作用，我们通过胚胎干细胞中的基因靶向产生了胃泌素缺陷小鼠。突变小鼠存活且可生育，无明显可见异常。然而，胃功能受到胃泌素损失的严重影响。基础胃酸分泌被取消，不能诱导组胺，卡巴胆碱，或胃泌素。组织学分析显示，在两种细胞类型的变化主要涉及酸分泌，壁和肠嗜铬样（ECL）细胞。壁细胞数量减少，缺乏H+-K+-腺苷三磷酸酶（H+-K+-ATPase）的未成熟细胞聚集。ECL细胞位于更靠近胃腺底部的位置，组胺酸脱羧酶的表达明显较低。胃泌素给药6天逆转了胃泌素缺乏的影响，导致成熟的，H+-K+-ATP酶阳性壁细胞的数量增加，并部分恢复酸分泌。结果表明，胃泌素对酸分泌系统的功能至关重要。
To further understand the role of the peptide hormone gastrin in the development and function of the stomach, we have generated gastrin-deficient mice by gene targeting in embryonic stem cells. Mutant mice were viable and fertile, without obvious visible abnormalities. However, gastric function was severely affected by the loss of gastrin. Basal gastric acid secretion was abolished and could not be induced by histamine, carbachol, or gastrin. Histological analysis revealed alterations in the two cell types primarily involved in acid secretion, parietal and enterochromaffin-like (ECL) cells. Parietal cells were reduced in number with an accumulation of immature cells lacking H+-K+-adenosin-etriphosphatase (H+-K+-ATPase). ECL cells were positioned closer to the base of the gastric glands, with markedly lower expression of histidine decarboxylase. Gastrin administration for 6 days reversed the effects of the gastrin deficiency, leading to an increase in the number of mature, H+-K+-ATPase-positive parietal cells and a partial restoration of acid secretion. The results show that gastrin is critically important for the function of the acid secretory system.