Adeyemi Edward O, Bastaki Salim A, Chandranath Irwin S, Hasan Mohammed Y, Fahim Mohammed, Adem Abdu
Department of Internal Medicine, UAE University, Al Ain, United Arab Emirates.
World J Gastroenterol. 2005 Jul 21;11(27):4154-60. doi: 10.3748/wjg.v11.i27.4154.
To investigate the effects of leptin (1-20 microg/kg) on acidified ethanol (AE)- and indomethacin (Indo)-induced gastric lesions in rats and compare it with ranitidine, lanso-prazole, and omeprazole and to determine its mechanisms of actions.
Gastric ulcers, which were approximately 1 mm in width, formed in the glandular portion of the gastric mucosa produced by oral administration of either AE or Indo were taken as ulcer index. The inhibitory effect of subcutaneous administration of leptin, two proton pump inhibitors (PPIs) lansoprazole and omeprazole, or H(2)-receptor antagonist ranitidine 30 min before AE or Indo was evaluated. A radioimmunoassay was used to determine the PGE(2) concentration in the homogenate of the glandular portion of the stomach. We performed histological study of the glandular stomach for the evaluation of total, acidic, and sulfated mucus content.
Subcutaneous administration of leptin, two PPIs lansoprazole and omeprazole or H(2)-receptor antagonist ranitidine 30 min before AE or Indo produced a dose-dependent and reproducible inhibition of gastric ulcers (GUs). This inhibition was found to be more potent than other antagonists used. In N(G)-nitro L-arginine methyl ester (L-NAME)-pretreated animals, the ulcer prevention ability of leptin in AE-induced ulcer was significantly reduced, compared to rats without L-NAME pretreatment. However, the ulcer prevention ability of leptin was not altered by L-NAME treatment in Indo-induced ulcers. Leptin produced a dose-dependent increase in PGE(2) level in the gastric glandular tissues. Leptin also increased mucus secretion.
The results of the present study show that leptin inhibits GU formation by AE or Indo in a dose-dependent and reproducible manner in rats. The results also suggest that leptin prevents ulcer formation by increasing the activities of the cyclo-oxygenase and/or nitric oxide pathways and by increasing mucus secretion.
研究瘦素（1 - 20微克/千克）对大鼠酸化乙醇（AE）和吲哚美辛（Indo）诱导的胃损伤的影响，并将其与雷尼替丁、兰索拉唑和奥美拉唑进行比较，同时确定其作用机制。
通过口服AE或Indo在胃黏膜腺部形成宽度约为1毫米的胃溃疡，以此作为溃疡指数。评估在给予AE或Indo前30分钟皮下注射瘦素、两种质子泵抑制剂（PPIs）兰索拉唑和奥美拉唑或H₂受体拮抗剂雷尼替丁的抑制作用。采用放射免疫分析法测定胃腺部匀浆中PGE₂浓度。对腺胃进行组织学研究以评估总黏液、酸性黏液和硫酸化黏液含量。
在给予AE或Indo前30分钟皮下注射瘦素、两种PPIs兰索拉唑和奥美拉唑或H₂受体拮抗剂雷尼替丁，可产生剂量依赖性且可重复的胃溃疡（GUs）抑制作用。发现这种抑制作用比使用的其他拮抗剂更强。在N⁰-硝基-L-精氨酸甲酯（L-NAME）预处理的动物中，与未用L-NAME预处理的大鼠相比，瘦素对AE诱导溃疡的预防能力显著降低。然而，在Indo诱导的溃疡中，L-NAME处理并未改变瘦素的溃疡预防能力。瘦素使胃腺组织中PGE₂水平呈剂量依赖性增加。瘦素还增加了黏液分泌。
本研究结果表明，瘦素在大鼠中以剂量依赖性和可重复的方式抑制AE或Indo诱导的GU形成。结果还表明，瘦素通过增加环氧化酶和/或一氧化氮途径的活性以及增加黏液分泌来预防溃疡形成。
