コレシストキニンA受容体欠損ラットの病態と適応 副題:自然発症CCK-A受容体遺伝子欠損動物および遺伝子ターゲッテイング動物による検討

我们检测了自然发生的CCK-A受体基因敲除大鼠的胃酸分泌。CCK-A受体基因敲除大鼠胃酸分泌在胃泌素或组胺刺激下显著高于对照组。CCK-A受体基因敲除大鼠胃组织中CCK-B/胃泌素受体基因表达水平较对照组高2倍，而H+/K+-ATPase和生长抑素基因表达水平无明显差异。组织学检查显示，CCK-A受体基因敲除大鼠的腺胃黏膜增厚，壁细胞增生肥大，而胃泌素和生长抑素免疫组织化学染色显示两株大鼠胃泌素染色相似，血浆胃泌素水平相近。CCK-A受体基因敲除大鼠的胃酸分泌增加被认为是由于壁细胞的增殖和肥大。我们还检测了CCK-A受体基因敲除大鼠的胃排空。CCK-A受体基因敲除大鼠的胃排空显著低于对照组。利血平的预先治疗显著增加了两个菌株的胃排空。然而，CCK-A受体基因敲除大鼠需要更高剂量的利血平才能产生与对照组相似的效果。提示CCK-A受体基因敲除大鼠胃排空延迟可能与交感神经功能增强有关。

We examined gastric acid secretion in naturally occurring CCK-A receptor gene knockout rats. Gastric acid secretion stimulated by gastrin or histamine was significantly higher in CCK-A receptor gene knockout rats than those of control rats. The levels of CCk-B/gastrin receptor mRNA in the stomach of CCK-A receptor gene knockout rats were 2-fold higher than those of control rats, although those of H+/K+-ATPase and somatostatin mRNA were not different. Histological examination reveald thickening of the mucosa of the glandular stomach, and hyperplasia and hypertrophy of parietal cells in CCK-A receptor gene knockout rats although immunohistochemistry of gastrin and somatostatin revealed the similar staining and the plasma level of gastrin were comparable for both strains. Increased acid secretion in CCK-A receptor gene knockout rats is considered to be due to hyperplasia and hypertrophy of parietal cells.We also examined gastric emptying in CCK-A receptor gene knockout rats. Gastric emptying was significantly reduced in CCK-A receptor gene knockout rats compared with that in control rats. The prior treatment of reserpine significantly enhanced gastric emptying in both strains. However, higher dose of reserpine was required in CCK-A receptor gene knockout rats to induce a similar effect to control rats. It is suggested that the delayed gastric emptying in CCK-A receptor gene knockout rats may be due to inceased sympathetic nerve function.The experiments using CCK-A receptor gene knockout mice as now in progress.