Učinci pentadekapeptida BPC 157, L-NAME i L-arginina na serijski prijelom rebara u štakora

Zukanović, Goran (2018) Učinci pentadekapeptida BPC 157, L-NAME i L-arginina na serijski prijelom rebara u štakora. PhD thesis, Sveučilište u Zagrebu.

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Abstract

Introduction: Rib fractures, in particular serial fractures (3 or more fractured ribs ipsilateral) have serious consequences on the human body and quality of life and represent an important medical and socioeconomic problem. Aim: To determine the effects of pentadecapeptide BPC 157, L-arginin and L-NAME on healing of serial rib fracture in rats. Materials and methods: After intraperitoneal anesthesia, in male Winstar albino rats was performed the vertical transection of 8-10 ribs of right hemithorax at the lateral edge of the paravertebral muscles. The pentadecapeptide BPC 157 was administered intraperitoneal or orally.It was applied intraperitoneal (doses of 10 μg/kg and 10 ng/kg) immediately following a surgical procedure and then once daily and the last application 24 h before sacrifice. Orally (0.16 μg/ml and 0.16 ng/ml, a total of 12 ml/day) was applied in drinking water, from waking up to the animal sacrifice. In order to test the interaction with the NO system, L-NAME (5 mg/kg/day i.p.) and/or L-arginin (100 mg/kg/day i.p.) were administered alone or with BPC 157 to specific animal groups. The control groups were treated with 0.9% NaCl i.p. or with pure drinking water p.o. The daily clinical status of the animal (respiration frequency, chest movement) was observed, and on 20th day, during the first sacrifice interval, aortic blood was taken to analyze the acid-base status and the calcium and phosphate serum levels. At the same time, the local finding was verified in the sense of the formation of endothoracic fascia and scar, and then the right hemitorax was taken for further radiographic and histological analysis. After 60 days, the animals were sacrificed for biomechanical testing. Results: Animals treated with BPC 157 did not show pathological alterations in acid-base status. Calcium and phosphate serum levels were normal in all animal groups. BPC 157 alone or in combination with L-arginin and/or L-NAME leads to earlier healing of the rib fracture and increased creations of callus without scarring and adhesions at the place of fracture, as confirmed by radiographic and histological analysis. Biomechanical testing has shown that bone tissue of animals treated with BPC 157 on the site of fractures is stronger. Conclusion: The pentadecapeptide BPC 157 leads to earlier healing of fractured ribs and formation of stronger bones at the site of the fractures, and this is the effect of interacting with the NO system. The positive effect of pentadecapeptida BPC 157 is achieved regardless of the way of administration (oral or intraperitoneal) and the administered dose (10 μg or 10 ng).

Abstract in Croatian

Uvod: Prijelomi rebara, posebice serijski prijelomi (3 ili više frakturirana rebra ipsilateralno) imaju teške posljedice na ljudski organizam i kvalitetu života te predstavljaju važan medicinski i socioekonomski problem. Cilj: Utvrditi učinke pentadekakpetida BPC 157, L-arginina i L-NAME na cijeljenje serijskog prijeloma rebara kod štakora. Materijali i metode: Nakon intraperitonealne anestezije, kod muških Wistar albino štakora učinila se vertikalna transekcija 8.-10. rebra desnog hemitoraksa na razini lateralog ruba paravertebralnih mišića. Pentadekapeptid BPC 157 primjenjivan je intraperitonealno ili peroralno. Intraperitonealno (doze od 10 μg/kg i 10 ng/kg) primjenjivan aplicirao se odmah po kirurškom zahvatu te nakon toga jednom dnevno, a zadnja aplikacija 24 h prije žrtvovanja. Peroralno (0.16 μg/ml i 0.16 ng/ml, ukupno 12 ml/dan) se primjenjivao u vodi za piće, od buđenja do žrtvovanja životinje. Da bi se testirala interakcija s NO sustavom, posebnim skupinama životinja aplicirali smo L-NAME (5 mg/kg/dan i.p.) i/ili L-arginin (100 mg/kg/dan i.p.) samostalno ili uz BPC 157. Kontrolne skupine tretirane su s 0.9% NaCl i.p. ili čistom vodom za piće p.o. Promatrao se svakodnevno klinički status životinje (frekvencija disanja, kretnje prsnog koša), a 20-ti dan, tijekom prvog intervala za žrtvovanje, uzimala se krv iz aorte za analizu acidobaznog statusa te odrađivanje serumskih vrijednosti kalcija i fosfata. U isto vrijeme verficirao se lokalni nalaz u smislu stvaranja priraslica endotorakalne fascije i ožiljka, a nakon toga se desni hemitoraks uzimao za daljnju radiografsku i histološku analizu. Nakon 60-tog dana životinje su žrtvovane radi biomehaničkog testiranja. Rezultati: Životinje tretirane s BPC 157 nisu pokazale patološka odstupanja u acidobaznom statusu. Serumske vrijednosti kalcija i fosfata bile su normalne kod svih skupina životinja. BPC 157 sam ili u kombinaciji s L-argininom i/ili L-NAME dovodi ranijeg cijeljenja prijeloma rebara te pojačanog stvaranja kalusa, bez stvaranja ožiljka i adhezija na mjestu fraktura, što je potvrđeno radiografskom i histološkom analizom. Biomehaničko testiranje pokazalo je da je koštano tkivo životinja tretiranih s BPC 157 na mjestu prijeloma jače. Zaključak: Pentadekapeptid BPC 157 dovodi do ranijeg cijeljenja frakturiranih rebara te formiranja jače kosti na mjestu prijeloma, a to je djelovanje u interakciji s NO sustavom. Pozitivan učinak pentadekapeptida BPC 157 ostvaruje se bez obzira na način primjene (per os ili intraperitonealno) i primjenjenu dozu (10 μg ili 10 ng).

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