Učinak pentadekapeptida BPC 157 na stvaranje ugrušaka u aortnoj anastomozi u štakora [Effect of pentadecapeptide BPC 157 on clot formation at aortal anastomosis in rats]

Hrelec Patrlj, Maša (2011) Učinak pentadekapeptida BPC 157 na stvaranje ugrušaka u aortnoj anastomozi u štakora [Effect of pentadecapeptide BPC 157 on clot formation at aortal anastomosis in rats]. PhD thesis, Sveučilište u Zagrebu.

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Abstract

Diseases that are the result of large vessels thrombosis are a subject of numerous scientific research programmes because of their clinical and economic aspect, but the thrombosis also happens in microcirculation. Microvascular thrombi are found in number of diseases and conditions like thrombocytopenic plethora, sepsis, disseminated intravascular coagulation etc. The significance of thrombosis and the importance of its prevention represent an important medical and economic goal. In this paper, we focused on impact of BPC 157 (in which we already proved citoprotectiv effect) on clot formation at the site of microvascular endothel injury cause by operation. Abdominal aorta was transected between renal and illiac arteries, and then anastomosised with Prolen 8/0 or 9/0 sutures. We operated a 100 animals, of which 50 received BPC 157 or saline right after the procedure, and the other half the same but after 24 hours. All the groups were measured the lower extremities strength, before and after procedure, and we did the walk analysis with the specific test. Histology specimens were harvested from all animals 24 hours after the surgery. All groups of animals that received BPC 157, weather it was microgram or nanogram concentration, or whether it was administered locally or by mouth, showed that there was no lot present in the histological aorta specimens. That result was also confirmed in functional test and walk analysis, where we noticed that the strength of the lower extremities was not impaired, compared to the values taken before the operation. On the other hand, control groups had statistically significantly different results. The ability to walk and lower extremities strength was significantly diminished after the surgery, and on histology specimens there was a clot in the aortal lumen. We showed that BPC 157 has a strong effect on clot prevention, when there is an endothel injury (transection and anastomosis), but most importantly his effect on already formed clot in animals who received BPC 157 24 hours after surgery.

Abstract in Croatian

Tromboze velikih krvnih žila tipično su predmet najbrojnijih istraživanja zbog velikom kliničkog i ekonomskog efekta, no tromboza zahvaća i mikrocirkulaciju. Mikrovaskularni trombi dokazani su u mnoštvu bolesti i stanja kao što su trombocitopenična purpura, sepsa, DIK i sl. Važnost tromboze i mogućnosti njenog spriječavanja predstavlja važan medicinski i ekonomski cilj. U ovom smo radu bili fokusirani na učinak pentadekapeptida BPC 157, u kojeg je vec dokazano citoprotektivno djelovanje, na stvaranje ugruška u krvnoj žili kojoj je endotel oštećen uslijed operativnog zahvata. Abdominalna aorta transecirana je u području između bubrežnih i ilijačnih arterija, te ponovno anastomozirana Prolen 8/0 ili 9/0 pojedinačnim šavima. Obrađeno je ukupno 100 životinja, od kojih je polovica primila BPC 157 odnosno fiziološku otopinu (kontrolne skupine) odmah nakon zahvata, a druga polovica isto nakon 24 sata. Svim skupinama mjerena je motorna snaga stražnjih ekstremiteta prije i nakon zahvata, te je analizirana kvaliteta hoda tzv. testom analize hodne pruge. U svih je skupina 24 sata nakon zahvata, po žrtvovanju, uzet tretirani odsječak aorte koji je patohistološki analiziran. Sve skupine koje su primile BPC 157, bilo da se radilo o mikrogramskoj ili nanongramskoj koncentraciji, odnosno lokalnoj ili peroralnoj primjeni pokazale su da njegov učinak u smislu nepostojanja ugruška na mjestu anastomoze. Navedeno se pozitivno odrazilo i u funkcionalnim testovima mišićne snage stražnjih ekstremiteta i analizi hodne pruge, gdje je uočeno da operativni zahvat nije utjecao na kvalitetu protoka u distalnoj aorti što je rezultiralo urednim hodom i jednakom snagom potiska straćnjih ekstremiteta kao i prije zahvata. U patohistološkoj analizi uočeno je da na u anastomoziranom dijelu aorte nije bio prisutan ugrušak. Sve navedeno statistički je značajno bilo različito u kontrolnim skupinama. Naime, u navedenima je analiza hodne pruge pokazala značajno pogoršanje hoda, u testu snage stražnjih ekstremiteta test je dao lošije rezultate nego prije zahvata, a na patohistologiji je operirani dio aorte bio većim dijelom zatvoren trombom. Ovim radom pokazan je visoka učinkovitost BPC 157 u spriječavanju nastanka ugruška na mjestu oštećenja endotela (transekcija i anastomoza), a poglavito njegov učinak na već postojeći ugrušak nakon operativnog zahvata u životinja u kojih je primjenjen 24 sata nakon operacije.

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