Baric Marko, Sever Anita Zenko, Vuletic Lovorka Batelja, Rasic Zarko, Sever Marko, Drmic Domagoj, Pavelic-Turudic Tatjana, Sucic Mario, Vrcic Hrvoje, Seiwerth Sven, Sikiric Predrag
Department of Surgery, School of Medicine, University of Zagreb, Salata 3b, 10000 Zagreb, Croatia.
Department of Pathology, School of Medicine, University of Zagreb, Salata 9, 10000 Zagreb, Croatia.
Life Sci. 2016 Mar 1;148:63-70. doi: 10.1016/j.lfs.2016.02.029. Epub 2016 Feb 9.
Rectovaginal fistula is a devastating condition providing more than 99% of patients for surgical treatment. We hypothesized that rectovaginal fistula may be healed by therapy with stable gastric pentadecapeptide BPC 157, in consistence with its initial clinical application and effect on external fistulas.
BPC 157 (10μg/kg or 10ng/kg) was given perorally, in drinking water (0.16μg/ml or 0.16ng/ml, 12ml/rat/day) till sacrifice, or alternatively, intraperitoneally, first application at 30min after surgery, last at 24h before sacrifice. Controls simultaneously received an equivolume of saline (5.0ml/kg ip) or water only (12ml/rat/day). The assessment (i.e., rectal and vaginal defect, fistula leakage, defecation through the fistula, adhesions and intestinal obstruction as healing processes) was at day 1, 3, 5, 7, 10, 14 and 21.
Regularly, rectovaginal fistulas exhibited poor healing, with both of the defects persisting, continuous fistula leakage, defecation through the fistula, advanced adhesion formation and intestinal obstruction. By contrast, BPC 157 given perorally or intraperitoneally, in μg- and ng-regimens rapidly improved the whole presentation, with both rectal and vaginal defects simultaneously ameliorated and eventually healed. The maximal instilled volume was continuously raised till the values of healthy rats were achieved, there were no signs of defecation through the fistula. A counteraction of advanced adhesion formation and intestinal obstruction was achieved. Microscopic improvement was along with macroscopic findings.
BPC 157 effects appear to be suited to induce a full healing of rectovaginal fistulas in rats.
直肠阴道瘘是一种严重疾病,超过99%的患者需要手术治疗。我们推测,稳定的胃十五肽BPC 157治疗可能治愈直肠阴道瘘,这与其最初的临床应用及对外瘘的疗效一致。
BPC 157(10μg/kg或10ng/kg)经口给予,溶于饮用水中(0.16μg/ml或0.16ng/ml,12ml/大鼠/天)直至处死,或者经腹腔给予,于术后30分钟首次给药,处死前24小时最后一次给药。对照组同时给予等体积的生理盐水(5.0ml/kg腹腔注射)或仅给予水(12ml/大鼠/天)。在第1、3、5、7、10、14和21天进行评估(即直肠和阴道缺损、瘘管渗漏、经瘘管排便、粘连和肠梗阻作为愈合过程)。
通常,直肠阴道瘘愈合不佳,缺损持续存在,瘘管持续渗漏,经瘘管排便,粘连形成进展,出现肠梗阻。相比之下,经口或经腹腔给予μg和ng方案的BPC 157可迅速改善整体情况,直肠和阴道缺损同时得到改善并最终愈合。最大灌胃体积持续增加直至达到健康大鼠的值,未出现经瘘管排便的迹象。实现了对粘连形成进展和肠梗阻的对抗作用。微观改善与宏观表现一致。
BPC 157的作用似乎适合诱导大鼠直肠阴道瘘完全愈合。