Vuksic Tihomir, Zoricic Ivan, Brcic Luka, Sever Marko, Klicek Robert, Radic Bozo, Cesarec Vedran, Berkopic Lidija, Keller Neike, Blagaic Alenka Boban, Kokic Neven, Jelic Ivan, Geber Juraj, Anic Tomislav, Seiwerth Sven, Sikiric Predrag
Department of Pharmacology, Medical Faculty, University of Zagreb, Salata 11, POB 916, 10000 Zagreb, Croatia.
Surg Today. 2007;37(9):768-77. doi: 10.1007/s00595-006-3498-9. Epub 2007 Aug 27.
Gastric pentadecapeptide BPC 157 (BPC 157), which has been shown to be safe in clinical trials for inflammatory bowel disease (PL-10, PLD-116, PL14736, Pliva, Croatia), may be able to cure intestinal anastomosis dehiscence. This antiulcer peptide shows no toxicity, is limit test negative, and a lethal dose is not achieved. It is stable in human gastric juice. In comparison with other standard treatments it is more effective for ulcers and various wounds, and can be used without a carrier needed for other peptides, both locally and systemically (i.e., perorally, parenterally). We studied the effectiveness of BPC 157 for ileoileal anastomosis healing in rats.
We assessed ileoileal anastomosis dehiscence macroscopically, histologically, and biomechanically (volume [ml] infused through a syringe-perfusion pump system (1 ml/10 s), and pressure [mmHg] to leak induction [catheter connected to a chamber and a monitor, at 10 cm proximal to anastomosis]), at 1, 2, 3, 4, 5, 6, 7, and 14 days. BPC 157 (10 microg, 10 ng, 10 pg/kg i.p. (or saline [5 ml/kg]) was first administered after surgery, while it was last given 24 h before either assessment or sacrifice.
Throughout the experiment, both higher doses of BPC 157 were shown to improve all parameters of anastomotic wound healing. The formation of adhesions remained slight, the blood vessels were filled with blood, and a mild intestinal passage obstruction was only temporarily observed. Anastomosis without leakage induces markedly higher volume and pressure values, with a continuous increase toward healthy values. From day 1, edema was markedly attenuated and the number of granulocytes decreased, while from days 4 or 5 necrosis decreased and granulation tissue, reticulin, and collagen formation substantially increased, thus resulting in increased epithelization.
This study showed BPC 157 to have a beneficial effect on ileoileal anastomosis healing in the rat.
胃十五肽BPC 157(BPC 157)在炎症性肠病的临床试验中已证明是安全的(PL - 10、PLD - 116、PL14736,普利瓦公司,克罗地亚),可能能够治愈肠吻合口裂开。这种抗溃疡肽无毒性,限度试验呈阴性,且未达到致死剂量。它在人胃液中稳定。与其他标准治疗方法相比,它对溃疡和各种伤口更有效,并且无需其他肽所需的载体即可局部和全身使用(即口服、胃肠外给药)。我们研究了BPC 157对大鼠回肠吻合口愈合的有效性。
我们在第1、2、3、4、5、6、7和14天,通过宏观、组织学和生物力学方法(通过注射器 - 灌注泵系统注入的体积[ml](1 ml/10 s)以及诱导渗漏的压力[mmHg] [导管连接到腔室和监测器,在吻合口近端10 cm处])评估回肠吻合口裂开情况。BPC 157(10微克、10纳克、10皮克/千克腹腔注射(或生理盐水[5 ml/千克])在手术后首次给药,而在评估或处死前24小时最后一次给药。
在整个实验过程中,较高剂量的BPC 157均显示可改善吻合口伤口愈合的所有参数。粘连形成轻微,血管充血,仅暂时观察到轻度肠道通过障碍。无渗漏的吻合口诱导出明显更高的体积和压力值,并持续向健康值增加。从第1天起,水肿明显减轻,粒细胞数量减少,而从第4天或第5天起坏死减少,肉芽组织、网状纤维和胶原形成显著增加,从而导致上皮化增加。
本研究表明BPC 157对大鼠回肠吻合口愈合有有益作用。