Gülnur ASLAN, HÜSEYİN FATİH GÜL, ENGİN ŞAHNA, Ebru ONALAN

Melatonin, Miyokardiyal İskemi-Reperfüzyon Hasarında Bax, Bcl2I1 ve XIAP Düzeylerini Etkileyerek Apoptotik Yolağı Düzenleyebilir

Amaç: İskemiden sonra kan akımının restorasyonu, iskemik dokunun canlılığını korumak için çok önemlidir. İskemik doku reperfüze edildiğinde, enzim degradasyonu, reaktif oksijen türlerinde aşırı artışa ve apoptoz gibi sekonder yaralanmalara neden olur. Pineal bezden salınan melatonin, önemli endojen antioksidanlardan biridir. Bu çalışmanın amacı; melatoninin, iskemi/reperfüzyon (I/R) hasarında proapoptotik B hücreli lenfoma 2 ile ilişkili X (Bax) ile antiapoptotik B hücreli lenfoma 2I1 (Bcl2I1) ve X' e bağımlı apoptoz inhibitörü (XIAP) düzeylerine etkisini araştırmaktır. Gereç ve Yöntem: Sıçanlar kontrol, I/R ve I/R+melatonin olmak üzere rastgele 3 gruba ayrıldı. Sol koroner arter 30 dk oklüze ve 120 dk reperfüze edilerek kardiyak hasar oluşturuldu. Melatonin i.p enjeksiyonu ile I/R’ den önce 10 gün boyunca uygulandı. Bax, Bcl2I1 ve XIAP seviyeleri ‘Eş zamanlı PCR’ ile analiz edildi. Bulgular: Doku Bax düzeyleri I/R hasarı ile 1,47 kat artarken, Bcl2I1 ve XIAP düzeyleri azaldı. Melatonin uygulaması, bu değişiklikleri inhibe ederek I/R kaynaklı miyokard hasarına karşı koruma sağladı. Sonuç: Antiapoptotik XIAP ve Bcl2I1 ve proapoptotik Bax, miyokardiyal I/R patolojisinde sinyal yollarında rol oynayabilir. Melatoninin koruyucu rolüne antiapoptotik aktivitelerinin katkısı olabilir.

Melatonin May Regulate Apoptotic Pathway Via Affecting Bax, Bcl2I1 and XIAP Levels in Myocardial Ischemia-Reperfusion Injury

Objective: Restoring blood flow after ischemia is very important for maintaining the viability of ischemic tissue. When ischemic tissue is reperfused, it causes enzyme degradation, excessive increase in reactive oxygen species and secondary injuries such as apoptosis. Melatonin released from the pineal gland is one of the important endogenous antioxidants. The aim of this study was to investigate the effect of melatonin on proapoptotic B-cell lymphoma 2 associated X (Bax) and antiapoptotic B-cell lymphoma 2I1 (Bcl2I1) and X-linked inhibitor of apoptosis (XIAP) levels by ischemia/reperfusion (I/R) injury. Material and Method: Rats were randomly divided into 3 groups as control, I/R, and I/R+melatonin. The left main coronary artery was occluded for 30 min followed by 120 min reperfusion. Melatonin was administrated by intraperitoneal injection during the last 10 days before I/R. Bax, Bcl2I1 and XIAP levels were analyzed by real time-PCR. Results: The tissue Bax levels increased 1,47 fold while Bcl2I1 and XIAP levels decreased with I/R injury. Melatonin administration showed protection against I/R induced myocardial injury by inhibiting all these changes. Conclusion: Antiapoptotic XIAP and Bcl2I1 and proapoptotic Bax may be involved in signaling pathways in the pathology of myocardial I/R, and the protective role of melatonin may be due to its antiapoptotic activities.

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