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胃十五肽BPC 157与大鼠短肠综合征

Gastric pentadecapeptide BPC 157 and short bowel syndrome in rats.

作者信息

Sever Marko, Klicek Robert, Radic Bozo, Brcic Luka, Zoricic Ivan, Drmic Domagoj, Ivica Mihovil, Barisic Ivan, Ilic Spomenko, Berkopic Lidija, Blagaic Alenka Boban, Coric Marijana, Kolenc Danijela, Vrcic Hrvoje, Anic Tomislav, Seiwerth Sven, Sikiric Predrag

机构信息

Department of Pharmacology, Medical School, University of Zagreb, Salata 11, 10000, Zagreb, Croatia.

出版信息

Dig Dis Sci. 2009 Oct;54(10):2070-83. doi: 10.1007/s10620-008-0598-y. Epub 2008 Dec 18.

Abstract

The gastric pentadecapeptide BPC 157, which was shown to be safe as an antiulcer peptide in trials for inflammatory bowel disease (PL14736, Pliva), successfully healed intestinal anastomosis and fistula in rat. Therefore, we studied for 4 weeks rats with escalating short bowel syndrome and progressive weight loss after small bowel resection from fourth ileal artery cranially of ileocecal valve to 5 cm beneath pylorus. BPC 157 (10 microg/kg or 10 ng/kg) was given perorally, in drinking water (12 ml/rat/day) or intraperitoneally (once daily, first application 30 min following surgery, last 24 h before sacrifice). Postoperatively, features of increasingly exhausted presentation were: weight loss appearing immediately regardless of villus height, twofold increase in crypt depth and fourfold increase in muscle thickness within the first week, jejunal and ileal overdilation, and disturbed jejunum/ileum relation. In contrast, constant weight gain above preoperative values was observed immediately with BPC 157 therapy, both perorally and parenterally, and villus height, crypt depth, and muscle thickness [inner (circular) muscular layer] also increased, at 7, 14, 21, and 28 days. Moreover, rats treated with pentadecapeptide BPC 157 showed not different jejunal and ileal diameters, constant jejunum-to-ileum ratio, and increased anastomosis breaking strength. In conclusion, pentadecapeptide BPC 157 could be helpful to cure short bowel syndrome.

摘要

胃十五肽BPC 157在炎症性肠病试验(PL14736,普利瓦公司)中被证明作为抗溃疡肽是安全的,它成功治愈了大鼠的肠吻合口和瘘管。因此,我们对小肠切除术后出现短肠综合征且体重逐渐减轻的大鼠进行了为期4周的研究,小肠切除范围是从回盲瓣的回肠动脉头侧至幽门下方5厘米处。BPC 157(10微克/千克或10纳克/千克)通过口服给予,添加到饮用水中(12毫升/大鼠/天)或腹腔注射(每天一次,首次给药在手术后30分钟,最后一次给药在处死前24小时)。术后,呈现出日益衰竭的特征有:无论绒毛高度如何,体重立即减轻,第一周内隐窝深度增加两倍,肌肉厚度增加四倍,空肠和回肠过度扩张,以及空肠/回肠关系紊乱。相比之下,口服和胃肠外给予BPC 157治疗后,立即观察到体重持续高于术前值增加,并且在第7、14、21和28天时,绒毛高度、隐窝深度和肌肉厚度(内环肌层)也增加。此外,用十五肽BPC 157治疗的大鼠空肠和回肠直径没有差异,空肠与回肠的比例恒定,吻合口破裂强度增加。总之,十五肽BPC 157可能有助于治愈短肠综合征。

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