Fukuhara Seiichiro, Suzuki Hidekazu, Masaoka Tatsuhiro, Arakawa Mamoru, Hosoda Hiroshi, Minegishi Yuriko, Kangawa Kenji, Ishii Hiromasa, Kitajima Masaki, Hibi Toshifumi
Department of Internal Medicine, Keio University School of Medicine,35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan.
Am J Physiol Gastrointest Liver Physiol. 2005 Jul;289(1):G138-45. doi: 10.1152/ajpgi.00298.2004. Epub 2005 Mar 18.
Ghrelin, produced and secreted by the A-like cells of the stomach, stimulates growth hormone secretion, gastric motility, and food intake. Cysteamine inhibits the release of somatostatin and induces the formation of duodenal ulcers in rats. The present study was conducted to investigate the dynamics of ghrelin secretion in rats treated with cysteamine. Male Wistar rats (7 wk old) were administered three doses of cysteamine (400 mg/kg) orally; at 50 h after the first dose, duodenal ulcers were induced, and the plasma level of somatostatin and gastric density of somatostatin-immunoreactive cells were significantly reduced. The plasma total and active ghrelin levels were significantly higher in the cysteamine-treated rats than in the control rats, whereas the gastric ghrelin levels, number of gastric ghrelin-immunoreactive cells, and preproghrelin mRNA expression levels were significantly lower. Even at the time points of 2 and 10 h after the first dose of cysteamine, at which time no significant ulcer formation or antral neutrophil accumulation was yet noted, a significant increase in the plasma ghrelin level and decrease in the gastric ghrelin level were observed. Furthermore, although lansoprazole treatment attenuated the duodenal ulceration induced by cysteamine, the increase in the plasma level of ghrelin could still be demonstrated. Because an inverse correlation was found between the plasma ghrelin and somatostatin levels, the inhibition of somatostatin secretion may be associated with the increased ghrelin secretion. In conclusion, an increase in the plasma ghrelin level precedes the formation of duodenal ulcers in rats treated with cysteamine.
胃内A样细胞产生并分泌的胃饥饿素可刺激生长激素分泌、胃蠕动及食物摄入。半胱胺可抑制生长抑素释放,并在大鼠中诱导十二指肠溃疡形成。本研究旨在探讨经半胱胺处理的大鼠胃饥饿素分泌的动态变化。雄性Wistar大鼠(7周龄)口服给予三剂半胱胺(400mg/kg);在首剂给药后50小时,诱导十二指肠溃疡形成,此时生长抑素的血浆水平及生长抑素免疫反应性细胞的胃密度显著降低。与对照大鼠相比,经半胱胺处理的大鼠血浆总胃饥饿素和活性胃饥饿素水平显著更高,而胃内胃饥饿素水平、胃内胃饥饿素免疫反应性细胞数量及前胃饥饿素mRNA表达水平显著更低。即使在首剂半胱胺给药后2小时和10小时这两个时间点,此时尚未观察到明显的溃疡形成或胃窦中性粒细胞聚集,但仍观察到血浆胃饥饿素水平显著升高及胃内胃饥饿素水平降低。此外,尽管兰索拉唑治疗减轻了半胱胺诱导的十二指肠溃疡,但仍可证明胃饥饿素血浆水平升高。由于发现血浆胃饥饿素与生长抑素水平呈负相关,生长抑素分泌的抑制可能与胃饥饿素分泌增加有关。总之,在经半胱胺处理的大鼠中,血浆胃饥饿素水平升高先于十二指肠溃疡形成。