Deneysel spinal kord iskemisi uygulanan sıçanlarda ardkoşullama ve/veya sitikolinin nöronal apopitozisteki nöron koruyucu etkilerinin incelenmesi
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Date
2009
Authors
Türkkan, Alper
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Publisher
Uludağ Üniversitesi
Abstract
Spinal kord iskemik hasarı spinal kordun kan akımında azalma ve/veya tam olarak kesilmesi nedeniyle oluşan, nöronlarda dejenerasyon ve kayıpla sonuçlanan olaylar zinciridir. Çalışmamızda iskemik olaylarda koruyucu etkisi gösterilmiş olan sitikolin ve iskemik ardkoşullamanın, spinal kord iskemisindeki nöronal hasarlanmayı azaltıcı etkilerinin apopitotik süreçle ilişkisini incelemek amaçlanmıştır. Spinal kord iskemisi için intratorasik girişimle sıçanlarda arkus aorta ve aynı anda subklavian arter kliplemesi yöntemi uygulandı. Çalışmamızda 42 adet erkek Sprague-Dawley sıçan (309±27 gr) kullanıldı. Deney grupları sham, spinal iskemi, sitikolin, ardkoşullama, ve ardkoşullama-sitikoin grupları olacak şekilde planlandı. Ardkoşullama uygulanan gruplarda klipleri çıkardıktan sonra 5 dakika reperfüzyon sonrası 1 dakika aralıklarla 6 siklus olarak ardkoşullama uygulandı. Sitikolin ve ardkoşullama-sitikolin grubuna iskemi öncesi 600 mmol/kg dozunda sitikolin inraperitoneal olarak verildi. Tüm sıçanlar reperfüzyondan 96 saat sonra sakrifiye edildi. İmmunohistokimyasal analiz için bcl-2, kaspaz 3, kaspaz 9 ve bax immün boyamaları yapıldı. Tüm gruplarda kan basıncı değerleri iskemi öncesi değerlere göre iskemi sonrasında anlamlı düşüş gösterdi. Gruplar arasında kaspaz 3, kaspaz 9, bax ve bcl-2 için immünohistokimyasal skorlama ortalamaları bakımından farklılık saptandı. İskemi uygunlanan gruplar (Grup 2, 3, 4 ve 5) sham grubu (Grup 1) ile karşılaştırıldığında kaspaz 3, kaspaz 9, bax ve bcl-2 seviyelerinde istatistiksel olarak anlamlı düzeyde artış saptandı. Kaspaz 9 ortalama skorları grup içi karşılaştırılmasında iskemi uygulanan grup 2’ de diğer gruplara göre anlamlı düzeyde artış saptandı. Bcl-2 ortalama skorlarının grup içi karşılaştırılmasında ise ardkoşullama ve sitikolin uygulanan grup 5’de istatistiksel olarak anlamlılık saptandı. iii Sitikolinin ardkoşullama ile kombine edilmesi apopitotik süreçte kaspaz yolağını inhibe ederek ve antiapopitotik proteinleri arttırarak nöronal koruma sağladığı düşünülmektedir.
İschemic spinal cord injury is a chain of events caused by reduction and/or cessation of spinal cord blood flow resulting in neuronal degeneration and loss. In our study it was aimed to present the relationship between the process of the neuronal injury-decreasing effects of citicoline and ischemic postconditioning which were proven to be effective on the apopitotic process. Synchronous arcus aorta and subclavian artery clipping method by intrathoracic approach for spinal cord ischemia in rats were performed. In our study, 42 male Sprague-Dawley rats (309±27 gr) were used. Experimental groups were planned as sham, spinal ischemia, citicoline, postconditioning and postconditioning-citicoline groups. Postconditioning were applied as 6 cycles by 1 minutes of ranges after 5 minutes of reperfusion following the clips were removed in groups that postconditioning were applied. 600 mmol/kg of citicoline was given by intraperitoneal route before ischemia in citicoline and postconditioning-citicoline groups. All rats were sacrified 96 hours after reperfusion. For immunohistochemical analysis, bcl-2, caspase 3, caspase 9 and bax immune staining were performed. The blood pressure values obtained at the onset of reperfusion were significantly lower than those of preischemic values. A difference in immunohistochemical scoring was detected between caspase 3, caspase 9, bax and bcl-2 groups. When compared the groups that ischemia were applied (Group 2, 3, 4, 5) with sham group (Group 1), a significant increase in caspase 3, caspase 9, bax and bcl-2 was detected. When compared the subgroups, average score of caspase 9 were found significantly higher in ischemia performed group 2. The average score of bcl-2 were also found significantly higher in postconditioning and citicoline applied group 5. It was thought that, combining citicoline with postconditioning provides v protection by inhibiting the caspase pathway and by increasing the antiapopitotic proteins.
İschemic spinal cord injury is a chain of events caused by reduction and/or cessation of spinal cord blood flow resulting in neuronal degeneration and loss. In our study it was aimed to present the relationship between the process of the neuronal injury-decreasing effects of citicoline and ischemic postconditioning which were proven to be effective on the apopitotic process. Synchronous arcus aorta and subclavian artery clipping method by intrathoracic approach for spinal cord ischemia in rats were performed. In our study, 42 male Sprague-Dawley rats (309±27 gr) were used. Experimental groups were planned as sham, spinal ischemia, citicoline, postconditioning and postconditioning-citicoline groups. Postconditioning were applied as 6 cycles by 1 minutes of ranges after 5 minutes of reperfusion following the clips were removed in groups that postconditioning were applied. 600 mmol/kg of citicoline was given by intraperitoneal route before ischemia in citicoline and postconditioning-citicoline groups. All rats were sacrified 96 hours after reperfusion. For immunohistochemical analysis, bcl-2, caspase 3, caspase 9 and bax immune staining were performed. The blood pressure values obtained at the onset of reperfusion were significantly lower than those of preischemic values. A difference in immunohistochemical scoring was detected between caspase 3, caspase 9, bax and bcl-2 groups. When compared the groups that ischemia were applied (Group 2, 3, 4, 5) with sham group (Group 1), a significant increase in caspase 3, caspase 9, bax and bcl-2 was detected. When compared the subgroups, average score of caspase 9 were found significantly higher in ischemia performed group 2. The average score of bcl-2 were also found significantly higher in postconditioning and citicoline applied group 5. It was thought that, combining citicoline with postconditioning provides v protection by inhibiting the caspase pathway and by increasing the antiapopitotic proteins.
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Keywords
Spinal kord iskemisi, Ardkoşullama, Apopitozis, Sitikolin, Spinal cord ischemia, Postconditioning, Apoptosis, Citicoline
Citation
Türkkan, A. (2009). Deneysel spinal kord iskemisi uygulanan sıçanlarda ardkoşullama ve/veya sitikolinin nöronal apopitozisteki nöron koruyucu etkilerinin incelenmesi. Yayınlanmamış uzmanlık tezi. Uludağ Üniversitesi Tıp Fakültesi.