Deneysel siyatik sinir hasarı modelinde üridin tedavisinin sinir rejenerasyonu ve skar dokusu oluşumu üzerine etkinliğinin araştırılması
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Date
2020
Authors
Khezri, Marzieh Karimi
Journal Title
Journal ISSN
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Publisher
Bursa Uludağ Üniversitesi
Abstract
Periferik sinir rejenerasyonu, günümüzde hala çözülemeyen bir sorun olarak karşımıza çıkmaktadır. Üridin majör pirimidin nükleozididir ve Kennedy yolağı aracılığıyla membran fosfolipid sentezinin bir prekürsörüdür. Çalışmamızın amacı; tek taraflı siyatik sinir hasarı sonrasında sistemik verilen üridin’in rejenerasyon ve skar dokusu oluşumu üzerine etkisinin araştırılmasıdır. Çalışmada 96 adet Sprague Dawley erişkin erkek sıçan kullanıldı. Denekler erken (4 grup) ve geç dönem (4 grup) olarak ayrıldı. Birinci grup hariç tüm gruplarda sağ siyatik sinir transeksiyon ve sütürasyon uygulandı. Birinci ve ikinci grupta salin (Sham ve Kontrol), üçüncüde Üridin 100mg/kg (U100), dördüncüde ise Üridin 500mg/kg (U500) intraperitoneal yolla 1 hafta boyunca günde bir kez enjeksiyonu yapıldı. Erken gruplar 1., geç ise 12. haftada sakrifiye edildi. Erken gruplarda apoptotik belirteç, oksidasyon hasarı ve antioksidatif savunma mekanizmaları incelendi. Geç dönemde ise siyatik fonksiyonel (SFI) ve elektrofizyolojik (EMG) testlerinden sonra siyatik sinirleri çıkarılarak akson iyileşmesi incelendi. U500 sıçanlarda anti-apoptoz etkisi kontrole göre anlamlı görüldü (p<0,05). U100 ve U500 gruplarında oksidasyon parametreleri kontrol gruba göre anlamlı düzeyde azalmış (p<0,001) ve anti-oksidasyon parametreleri yükselmiştir (p<0,001). U500 grubunda, kontrol gruba göre sinir ayrılabilirliği açısından anlamlı olarak daha iyi sonuçlar saptandı (p=0,002). 6. ve 12. haftadaki SFI U100 ve U500 gruplarında kontrole göre belirgin iyileşme saptandı (p<0,001). 12.haftada EMG analizlerinde U500 ile tedavi edilen grupta kontrol ve U100 gruplarına göre yüksek amplitüd değerleri saptandı (p<0,001). Akson sayısı açısından; U100 ve U500 gruplarında kontrole göre anlamlı istatistiksel artış görüldü (p<0,05). Sonuçlarımız, sistemik uygulanan üridinin doza bağımlı olarak anti-apoptotik ve anti-oksidatif etkinliğe sahip olduğunu göstermektedir. Ayrıca SFI iyileşme, sinir dokusu rejenerasyonunda artış, perinöral skar dokusunda iii azalma, EMG latansında kısalma, sinir adhezyon ve seperabilite skorlarında iyileşme ve miyelinli akson sayısında anlamlı artışlar tespit edilmiştir. Bulgularımıza göre üridin periferik sinir hasarında iyileşmeyi artırıcı etkinlik göstermektedir.
Peripheral nerve regeneration is still unsolved problem in regenerative medicine. Uridine as bloodstream major pyrimidine nucleoside is a precursor of membrane phospholipid synthesis via the Kennedy pathway. Our purpose is investigation the effect of systemic uridine administration.after unilateral sciatic nerve injury on regeneration and scar tissue formation. In this study, 96 adult male Sprague Dawley rats were used. They were divided into two main groups as early (4 groups) and late (4 groups). Right sciatic nerve transection and suturing were performed in all groups except first one. Intraperitoneally once a day for a week, saline in the first and second groups (Sham and Control), Uridin 100mg/kg (U100) in the third, Uridine 500mg/kg (U500) in the fourth groups, had been injected. Early groups were sacrificed at the 1st and late at the 12th week. In early groups, apoptotic marker, oxidation damage and antioxidative defense mechanisms were examined. In the late ones, after the sciatic functional (SFI) and electrophysiological (EMG) tests, the sciatic nerves were removed and axon healing was examined. Anti-apoptosis effect was found to be significant in U500 rats compared to control (p <0.05). In the U100 and U500 groups, oxidation parameters decreased significantly compared to control (p <0.001) and anti-oxidation parameters increased (p <0.001). In the U500 group, significantly better results were found in terms of nerve separability than control (p=0.002). In the 6th and 12th week SFI U100 and U500 groups showed significant improvement compared to control (p <0.001). At 12th week EMG analysis showed high amplitude values in U500 group compared to control and U100 (p<0.001). In terms of the number of myelinated axons; v statistically increase observed in U100 and U500 groups compared to control (p <0.05). Systemically Uridine administeration has anti-apoptotic and anti-oxidative effects, especially in a dose-dependent manner. In addition, SFI improvement, nerve tissue regeneration, perineural scar tissue decrease, shortening of EMG latency, nerve seperability score improvement and myelinated axones increase were observed.
Peripheral nerve regeneration is still unsolved problem in regenerative medicine. Uridine as bloodstream major pyrimidine nucleoside is a precursor of membrane phospholipid synthesis via the Kennedy pathway. Our purpose is investigation the effect of systemic uridine administration.after unilateral sciatic nerve injury on regeneration and scar tissue formation. In this study, 96 adult male Sprague Dawley rats were used. They were divided into two main groups as early (4 groups) and late (4 groups). Right sciatic nerve transection and suturing were performed in all groups except first one. Intraperitoneally once a day for a week, saline in the first and second groups (Sham and Control), Uridin 100mg/kg (U100) in the third, Uridine 500mg/kg (U500) in the fourth groups, had been injected. Early groups were sacrificed at the 1st and late at the 12th week. In early groups, apoptotic marker, oxidation damage and antioxidative defense mechanisms were examined. In the late ones, after the sciatic functional (SFI) and electrophysiological (EMG) tests, the sciatic nerves were removed and axon healing was examined. Anti-apoptosis effect was found to be significant in U500 rats compared to control (p <0.05). In the U100 and U500 groups, oxidation parameters decreased significantly compared to control (p <0.001) and anti-oxidation parameters increased (p <0.001). In the U500 group, significantly better results were found in terms of nerve separability than control (p=0.002). In the 6th and 12th week SFI U100 and U500 groups showed significant improvement compared to control (p <0.001). At 12th week EMG analysis showed high amplitude values in U500 group compared to control and U100 (p<0.001). In terms of the number of myelinated axons; v statistically increase observed in U100 and U500 groups compared to control (p <0.05). Systemically Uridine administeration has anti-apoptotic and anti-oxidative effects, especially in a dose-dependent manner. In addition, SFI improvement, nerve tissue regeneration, perineural scar tissue decrease, shortening of EMG latency, nerve seperability score improvement and myelinated axones increase were observed.
Description
Keywords
Apoptozis, Periferik sinir, Üridin, Rejenerasyon, Skar, Apoptosis, Peripheral nerve, Uridine, Regeneration, Scar
Citation
Khezri, M. K. (2020). Deneysel siyatik sinir hasarı modelinde üridin tedavisinin sinir rejenerasyonu ve skar dokusu oluşumu üzerine etkinliğinin araştırılması. Yayınlanmamış tıpta uzmanlık tezi. Bursa Uludağ Üniversitesi Tıp Fakültesi.