Učinak pentadekapeptida BPC 157 na cijeljenje rektovaginalnih fistula u štakora [The effect of pentadecapeptide BPC 157 on healing of rectovaginal fistulas in rats]

Barić, Marko (2017) Učinak pentadekapeptida BPC 157 na cijeljenje rektovaginalnih fistula u štakora [The effect of pentadecapeptide BPC 157 on healing of rectovaginal fistulas in rats]. PhD thesis, Sveučilište u Zagrebu.

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Abstract

Aim. Recto-vaginal fistula is a devastating condition providing more than 99% of patients for surgical treatment. We hypothesized that rectovaginal fistulae may be healed by therapy with stable gastric pentadecapeptide BPC 157, in consistence with its initial clinical application and effect on external fistulas. Materials and Methods. BPC 157 (10 μg/kg or 10 ng/kg) was given perorally, in drinking water (0.16 μg/ml or 0.16 ng/ml, 12 ml/rat/day) till sacrifice, or alternatively, intraperitoneally, first application at 30 min after surgery, last at 24h before sacrifice. Controls simultaneously received an equivolume of saline (5.0 ml/kg ip) or water only (12 ml/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. Results. 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 healhty 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. Conclusion. BPC 157 effects appear to be suited to induce a full healing of rectovaginal fistulas in rats.

Abstract in Croatian

Cilj. Rektovaginalna fistula je poražavajuće stanje kod kojeg više od 99% pacijenata zahtijeva kirurško liječenje. Pretpostavili smo da rektovaginalne fistule mogu biti izliječene terapijom stabilnim želučanim pentadekapeptidom BPC 157, u dosljednosti s dosadašnjom kliničkom primjenom i djelovanjem na vanjske fistule. Materijali i metode. BPC 157 (10 μg/kg ili 10 ng/kg) je dan peroralno, u vodi za piće (0,16 μg/ml ili 0,16 ng/ml, 12 ml/štakor/dan) do žrtvovanja, ili alternativno, intraperitonealno, prvom aplikacijom 30 min nakon operacije, posljednjom 24 h prije žrtvovanja. Kontrole su također dobile ekvivolumnu otopinu soli (5,0 ml/kg i.p.) ili samo vode (12 ml/štakor/dan). Procjena (tj. rektalni i vaginalni defekt, propuštanje fistule, defekacija kroz fistulu, priraslice i crijevna opstrukcija tijekom procesa cijeljenja) je bila 1, 3, 5, 7, 10, 14 i 21 dan. Rezultati. Redovito rektovaginalne fistule pokazuju loše cijeljenje, uz prisutnost oba defekta, kontinuiranim propuštanjem fistule, defekacijom kroz fistulu, nastajanje priraslica i crijevnu opstrukciju. Suprotno, BPC 157 dan peroralno ili intraperitonealno u μg i ng dovodi brzo do poboljšanja, sa obje i rektalne i vaginalne strane dovodi istovremeno do poboljšanja i na kraju izlječenja. Maksimalni apliciran volumen kontinuirano je podizan do postignuća vrijednosti kao u zdravih štakora, nije bilo nikakvih znakova defekacije kroz fistule. Supresija nastajanja priraslica i crijevne opstrukcije je postignuta. Zapaženo je poboljšanje mikroskopskih i makroskopskih nalaza. Zaključak. Učinci BPC-a 157 čine se povoljni u induciranju potpunog cijeljenja rektovaginalnih fistulama u štakora.

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