Enhanced ghrelin secretion in rats with cysteamine-induced duodenal ulcers
Enhanced ghrelin secretion in rats with cysteamine-induced duodenal ulcers
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DOI：
10.1152/ajpgi.00298.2004
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发表时间：
2005-07-01
影响因子：
4.5
通讯作者：
Hibi, T
中科院分区：
文献类型：
--
作者：
Fukuhara, S;Suzuki, H;Hibi, T
胃促生长素由胃的a样细胞产生和分泌，刺激生长激素分泌、胃运动和食物摄入。半胱胺抑制生长抑素的释放，诱导大鼠十二指肠溃疡的形成。本研究旨在探讨半胱胺对大鼠胃饥饿素分泌的影响。雄性Wistar大鼠（7周龄）口服3次半胱胺（400 mg/kg）；第一次给药后50 h诱导十二指肠溃疡，血浆中生长抑素水平和胃中生长抑素免疫反应细胞密度显著降低。半胱胺处理大鼠血浆总胃饥饿素和活性胃饥饿素水平显著高于对照组，而胃饥饿素水平、胃饥饿素免疫反应细胞数量和胃饥饿素前原mRNA表达水平显著低于对照组。即使在第一次半胱胺给药后2和10 h的时间点，在没有明显溃疡形成和胃壁中性粒细胞积累的情况下，血浆胃饥饿素水平明显升高，胃饥饿素水平明显下降。此外，尽管兰索拉唑治疗可以减轻半胱胺引起的十二指肠溃疡，但血浆ghrelin水平仍可升高。由于发现血浆ghrelin与生长抑素水平呈负相关，抑制生长抑素分泌可能与ghrelin分泌增加有关。总之，半胱胺处理的大鼠在十二指肠溃疡形成之前血浆胃饥饿素水平升高。
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.