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大鼠幽门括约肌原发性功能障碍后的持续性食管炎及胃十五肽BPC 157的治疗潜力

Prolonged esophagitis after primary dysfunction of the pyloric sphincter in the rat and therapeutic potential of the gastric pentadecapeptide BPC 157.

作者信息

Dobric Ivan, Drvis Petar, Petrovic Igor, Shejbal Drazen, Brcic Luka, Blagaic Alenka Boban, Batelja Lovorka, Sever Marko, Kokic Neven, Tonkic Ante, Zoricic Ivan, Mise Sandro, Staresinic Mario, Radic Bozo, Jakir Ana, Babel Jaksa, Ilic Spomenko, Vuksic Tihomir, Jelic Ivan, Anic Tomislav, Seiwerth Sven, Sikiric Predrag

机构信息

Department of Pharmacology, Medical School, University of Zagreb, Croatia.

出版信息

J Pharmacol Sci. 2007 May;104(1):7-18. doi: 10.1254/jphs.fp0061322. Epub 2007 Apr 24.

DOI:10.1254/jphs.fp0061322
PMID:17452811
Abstract

Seven or fourteen days or twelve months after suturing one tube into the pyloric sphincter (removed by peristalsis by the seventh day), rats exhibit prolonged esophagitis with a constantly lowered pressure not only in the pyloric, but also in the lower esophageal sphincter and a failure of both sphincters. Throughout the esophagitis experiment, gastric pentadecapeptide BPC 157 (PL 14736) is given intraperitoneally once a day (10 microg/kg, 10 ng/kg, last application 24 h before assessment), or continuously in drinking water at 0.16 microg/ml, 0.16 ng/ml (12 ml/rat per day), or directly into the stomach 5 min before pressure assessment (a water manometer connected to the drainage port of a Foley catheter implanted into the stomach either through an esophageal or duodenal incision). This treatment alleviates i) the esophagitis (macroscopically and microscopically, at either region or interval), ii) the pressure in the pyloric sphincter, and iii) the pressure in the lower esophageal sphincter (cmH2O). In the normal rats it increases lower esophageal sphincter pressure, but decreases the pyloric sphincter pressure. Ranitidine, given using the same protocol (50 mg/kg, intraperitoneally, once daily; 0.83 mg/ml in drinking water; 50 mg/kg directly into the stomach) does not have an effect in either rats with esophagitis or in normal rats.

摘要

将一根管子缝合到幽门括约肌中(到第7天时已被蠕动移除)7天、14天或12个月后,大鼠不仅幽门括约肌,而且食管下括约肌压力持续降低,且两个括约肌均功能失调,从而出现持续性食管炎。在整个食管炎实验过程中,每天腹腔注射一次胃十五肽BPC 157(PL 14736)(10微克/千克,10纳克/千克,在评估前24小时最后一次给药),或以0.16微克/毫升、0.16纳克/毫升的浓度持续添加到饮用水中(每只大鼠每天12毫升),或在压力评估前5分钟直接注入胃内(通过食管或十二指肠切口将连接到植入胃内的Foley导管引流口的水柱压力计)。这种治疗可缓解:i)食管炎(无论是在宏观还是微观层面,在任何区域或时间段),ii)幽门括约肌压力,以及iii)食管下括约肌压力(厘米水柱)。在正常大鼠中,它会增加食管下括约肌压力,但会降低幽门括约肌压力。按照相同方案给予雷尼替丁(50毫克/千克,腹腔注射,每日一次;饮用水中浓度为0.83毫克/毫升;50毫克/千克直接注入胃内),对患有食管炎的大鼠或正常大鼠均无作用。

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