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作 者:许庆华[1] 李宗河[1] 黄菲菲[1] 王昉彤[1]
机构地区:[1]四川抗菌素工业研究所药理学教研室,成都610052
出 处:《中国新药杂志》2015年第8期917-923,共7页Chinese Journal of New Drugs
摘 要:目的:比较雷贝拉唑钠右旋体、左旋体和消旋体对H+,K+-ATP酶活性抑制作用的强弱,以及体内抗实验性大鼠胃溃疡作用的强弱。方法:取正常SD大鼠胃黏膜,体外测定雷贝拉唑钠右旋体、左旋体以及消旋体对H+,K+-ATP酶的抑制作用。建立水应激型、消炎痛刺激、幽门结扎法3种大鼠胃溃疡模型,观察三者对实验性胃溃疡形成的影响。并在水应激模型中取SD大鼠胃黏膜测定体内对H+,K+-ATP酶活性的影响。结果:右旋体、左旋体以及消旋体体外抑制H+,K+-ATP酶的活性未见明显差异;但在水应激模型中体内对H+,K+-ATP酶活性有抑制作用,且雷贝拉唑钠右旋体>左旋体和消旋体。与模型组比较,雷贝拉唑钠右旋体对3种SD大鼠实验性胃溃疡具有明显的抑制作用(P<0.01或P<0.05),效果优于消旋体和左旋体,能显著抑制胃溃疡的发生。结论:体外H+,K+-ATP酶活性抑制测定结果,三者之间抑制效果没有明显差异;但体内酶活性抑制作用雷贝拉唑钠右旋体强于消旋体和左旋体。等剂量雷贝拉唑钠右旋体对3种大鼠胃溃疡的抗溃疡作用强于消旋体和左旋体。Objective: To compare the inhibiting effects of rabeprazole sodium and its isomers on H ^+ , K ^+ ATPase activity, and experimental gastric ulcer in rats. Methods: The anti-ulcer effects of rabeprazole and its isomers were evaluated in three different rat models of gastric ulcer, namely pyloric ligation, indomethacin stimulation, and water stress. H^+ , K ^+ -ATPase activity of gastric mucosa was determined in normal or water stress rats. Results: Compared with ulcer control, dexrabeprazole significantly inhibited the development of gastric ulcer in three models (P 〈0.01 or P 〈 0.05), and its effect was more potent than the S ( - )-isomer and rabeprazole. Dexrabeprazole, rabeprazole and S( - )-isomer had similar inhibiting effects on H ^+ , K ^+ -ATPase activity in vitro. However, dexrabeprazole had an inhibiting effect on H ^+ , K ^+ -ATPase activity more potent than rabeprazole and the S( -)-isomer in vivo. Conclusion: Three drugs have similar effects on H^+, K^+-ATPase activity in vitro; but dexrabeprazole is more potent than rabeprazole and the S( - )-isomer in vivo. Dexrabeprazole is superior to rabeprazole and S( - )-isomer at the same doses for inhibiting gastric ulcer in three rat models.
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