Department of Pharmacology, Faculty of Medicine & Health Sciences, UAE University, Al Ain, United Arab Emirates.
Mol Cell Biochem. 2011 Mar;349(1-2):205-12. doi: 10.1007/s11010-010-0675-3. Epub 2010 Nov 30.
Combining restraint with cold temperature (4°C) consistently induces gastric ulceration in rats after 3.5 h. The cold restraint-stress (CRS) method provides a suitable model for acute ulcer investigations. This study compares the antiulcer activities of lansoprazole (a proton pump inhibitor), PD-136450 (CCK(2)/gastrin receptor antagonist) and ranitidine (histamine H(2) receptor antagonist) on CRS-induced gastric ulcers in rats. The results have shown that lansoprazole, which is a potent anti-secretory agent, provides complete protection in this model of ulcer formation. The use of indomethacin pretreatment to inhibit the prostaglandin (PG) synthesis and N(G)-nitro L-arginine methyl ester (L-NAME) pretreatment to inhibit nitric oxide synthase did not alter the lansoprazole-induced inhibition of ulcer index obtained in the untreated Wistar rats indicating that these two systems were not involved in the activation of lansoprazole. PD-136450, an effective anti-secretory agent against gastrin- but not dimaprit-induced stimulation, evoked a dose-dependent inhibition of CRS-induced gastric ulcers. The results show that both PG and nitric oxide pathways can influence the inhibitory effect of PD-136450 against CRS-induced gastric ulcer. The antiulcer activities of both lansoprazole and PD-136450 were compared to that of ranitidine. The results showed that ranitidine was more potent than lansoprazole and PD-136450 in inhibiting CRS-induced gastric ulcers and its effect was shown to be influenced by PG as well as nitric oxide synthase. The results of this study have demonstrated that although lansoprazole, PD-136450 and ranitidine were protective against CRS-induced gastric ulcers, the antiulcer activities of PD-136450 and ranitidine involved both PG and nitric oxide pathways, while lansoprazole acted independently of these two systems during CRS.
将束缚与低温（4°C）相结合可在 3.5 小时后持续诱发大鼠胃溃疡。冷束缚应激（CRS）方法为急性溃疡研究提供了合适的模型。本研究比较了兰索拉唑（质子泵抑制剂）、PD-136450（CCK（2）/胃泌素受体拮抗剂）和雷尼替丁（组胺 H2 受体拮抗剂）对 CRS 诱导的大鼠胃溃疡的抗溃疡活性。结果表明，兰索拉唑是一种有效的抗分泌剂，在这种溃疡形成模型中提供了完全的保护。使用吲哚美辛预处理抑制前列腺素（PG）合成和 N（G）-硝基 L-精氨酸甲酯（L-NAME）预处理抑制一氧化氮合酶不会改变未处理的 Wistar 大鼠中兰索拉唑诱导的溃疡指数抑制作用，表明这两个系统未参与兰索拉唑的激活。PD-136450 是一种有效的抗胃泌素但不是二甲普里诱导刺激的分泌剂，可引起 CRS 诱导的胃溃疡的剂量依赖性抑制。结果表明，PG 和一氧化氮途径都可以影响 PD-136450 对 CRS 诱导的胃溃疡的抑制作用。兰索拉唑和 PD-136450 的抗溃疡活性与雷尼替丁进行了比较。结果表明，雷尼替丁比兰索拉唑和 PD-136450 更能抑制 CRS 诱导的胃溃疡，其作用受到 PG 以及一氧化氮合酶的影响。本研究的结果表明，尽管兰索拉唑、PD-136450 和雷尼替丁对 CRS 诱导的胃溃疡具有保护作用，但 PD-136450 和雷尼替丁的抗溃疡活性涉及 PG 和一氧化氮途径，而兰索拉唑在 CRS 期间独立于这两个系统起作用。
