İskemi-Reperfüzyon Hasarı ve Oksidatif Stress İlişkisine Biyokimyasal Bakış

Oguzhan Ozcan, Huseyin Erdal, Zafer Yonden
2.095 1.022

Öz


İskemi-reperfüzyon hasarı; miyokard infarktüsü, serebrovasküler infarkt, organ transplantasyonları, kardiyopulmoner resusitasyon, trombolitik tedavi ve hemorajik şok gibi birçok klinik durumda halen hastalar için yüksek morbidite ve mortalite nedenidir. Dokuya giden kan akımının azalması ve oksijen yetersizliği ile başlayan iskemik doku hasarı, reperfüzyon sağlandığında hasarlanmış dokuların yeniden oksijenasyonu ile artarak devam eder. Hücrelerdeki mitokondriyel ATP üretiminin azalması hücre içi metabolizmanın anaerobik yöne kaymasına ve hücre içi asidoza sebep olur. ATP bağımlı Na-K iyon pompalarının yavaşlaması, hücre içi hidrojen artışına yol açar. Artmış hidrojen yükünü dengelemek için ATP bağımlı olmayan Na-Ca pompası intraselüler kalsiyum miktarını artırır. Artmış kalsiyum yükü ise birçok sitozolik proteazı aktive eder. Hücre içi proteaz aktivasyonu ve reperfüzyonla dokuların yeniden oksijenasyonu ise sonuçta hidroksil radikali (OH•), süperoksit radikali (O2•−) ve hidrojen peroksit H2O2 gibi reaktif oksijen türleri (ROS) ile peroksinitrit (ONOO-) gibi reaktif nitrojen türlerinin (RNS) üretimine yol açan kritik biyokimyasal yolakları hızlandırır. Ayrıca artmış serbest radikallerin neden olduğu inflamasyon, bölgeye inflamatuvar hücrelerin toplanmasını tetikler. Endotelyal hücrelerle başta polimorf çekirdekli lökositler olmak üzere inflamatuvar hücreler arasındaki etkileşimler, birçok sitokinin salınmasına ve iskeminin yol açtığı hasarın reperfüzyonla genişlemesine yol açar. Ksantin oksidaz, nitrik oksit sentaz, mitokondrilerde bulunan elektron transport zinciri ve fagositlerdeki solunumsal patlamadan sorumlu NADPH oksidaz, ROS ve RNS üretiminden sorumlu başlıca mekanizmalardır. Sonuçta oluşan serbest radikaller hücre membranlarındaki lipit yapılar, hücre içi yapısal ve fonksiyonel proteinler ve genetik materyal gibi önemli makromoleküllere zarar vererek hücre hasarı veya ölümüne yol açarlar. İskemi-reperfüzyonda hasar oluşumu oldukça kompleks bir süreç olup, bu derlemede başlıca oksidatif stres ile ilişkisi ele alınmıştır.

Anahtar kelimeler: İskemi-reperfüzyon hasarı, oksidatif stres, reaktif oksijen türleri


Anahtar kelimeler


İskemi-reperfüzyon hasarı, oksidatif stres, reaktif oksijen türleri

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DOI: http://dx.doi.org/10.17944/mkutfd.54113

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