İSKEMİK ÖNKOŞULLAMA VE N-ASETİL SİSTEİN'İN SIÇAN İSKELET KASI İSKEMİ- REPERFÜZYONUNDAKİ İNFLAMATUAR SÜREÇ ÜZERİNE OLAN ETKİLERİ

Year 2012, Volume: 13 Issue: 2, 15 - 20, 01.08.2012

Uğur Gürcün Tünay Kurtoğlu Çiğdem Yenisey Erdem Özkısacık Mehmet Boğa Berent Dişçigil

Abstract

AMAÇ: İskelet kasındaki iskemi-reperfüzyon (İ/R) hasarı, inflamatuar mekanizmanın da önemli rol oynadığı karmaşık bir süreçtir. İskemik önkoşullama (İÖK) ve reaktif oksijen radikal tutucusu bir ajan olan Nasetilsistein'in (NAC), İ/R hasarını azaltıcı etkileri olduğu bilinmektedir. Bu çalışmada, İÖK ve NAC'ın İ/R hasarındaki inflamatuar süreç üzerine olan etkilerini, ayrıca bu iki yöntemin birlikte kullanımının bu süreç üzerinde nasıl bir etki oluşturduğunu değerlendirmeyi amaçladık.GEREÇ ve YÖNTEM: Otuz beş adet Sprague-Dawley cinsi sıçan her birinde yedi sıçan bulunan beş farklı gruba ayrıldı. Sham grubunda infrarenal abdominal aort izole edildi ancak iskemi oluşturulmadı. Kontrol grubunda infrarenal abdominal aort 120 dakika boyunca klempe edilerek alt ekstremitelerde iskemi, ardından 50 dakika süreyle reperfüzyon gerçekleştirildi. İÖK grubunda, İ/R öncesinde üç siklus şeklinde 10'ar dakikalık iskemi ve reperfüzyon uygulandı. NAC grubunda iskemik periyodun sonunda 20 mg/kg NAC intravenöz bolus olarak verildi ve reperfüzyon süresince 20 mg/kg/saat dozunda idamesi sağlandı. NAC+İÖK grubunda, İÖK sırasında aynı dozda ve eşit sürede NAC uygulandı. Tüm gruplarda reperfüzyon periyodunun sonunda serum proinflamatuar sitokin (IL-1β, IL-6 ve TNF-α) değerlerinin belirlenebilmesi için kan örnekleri alınarak sıçanlar sakrifiye edildi.BULGULAR: Çalışmada incelenen tüm serum sitokin düzeylerinin kontrol grubunda sham grubuna göre anlamlı yüksek olduğu tespit edildi. Çalışma gruplarında da sitokin düzeylerinin sham grubuna göre ılımlı yüksek bulunmasına karşın, kontrol grubuna göre her üç grupta da belirgin düşük bulunduğu gözlemlendi. Çalışma gruplarının birbirleriyle olan karşılaştırmasında belirgin bir farklılık saptanmadı.SONUÇ: Bu bulgular iskelet kasındaki İ/R hasarlanmasında inflamasyonun önemli bir rol oynadığını göstermektedir. Sonuçlarımız İÖK ve NAC'ın iskelet kasındaki İ/R aracılı inflamatuar süreçte faydalı etkileri olduğunu düşündürmektedir. Serum proinflamatuar sitokin seviyesi açısından iki yöntemin birbirine göre belirgin bir üstünlüğü bulunmadığı ve birlikte kullanımlarının ek bir fayda sağlamadığı gözlemlenmiştir

Keywords

İskemi-reperfüzyon, iskemik önkoşullama, N-asetilsistein, sitokin

Influence of Ischemic Preconditioning and N-Acetylcysteine on Inflammatory Process in Rat Skeletal Muscle Ischemia-Reperfusion

Abstract

OBJECTIVE: Skeletal muscle ischemia-reperfusion (I/R) injury is a complex process in which the inflammatory mechanisms play important role. Ischemic preconditioning (IPC) and reactive oxygen radical scavenger N-acetylcsyteine (NAC) have been shown to attenuate I/R injury. We aimed to investigate the effects of IPC and NAC on I/R induced inflammation and the influence of synchronous application. MATERIALS and METHODS: Thirty-five Sprague-Dawley rats were randomly assigned to five groups. In sham group, infrarenal aorta was isolated without induction of ischemia. In control group, ischemia was induced for 120 min, followed by reperfusion for 50 minutes. In IPC group, three cycles of 10 min ischemia, followed by 10 min reperfusion was formed preceding I/R. NAC group rats received an intravenous NAC (20 mg/kg) at the end of ischemic period and a maintenance dose of 20mg/kg/hr throughout the reperfusion. In IPC+NAC group, an equal amount of NAC was administered in an identical time period during IPC. Blood samples were obtained at the end of reperfusion for analysis of IL-1β, IL-6 and TNF-α level then rats were sacrificed. RESULTS: All serum cytokine levels which were analyzed in this study were found to be significantly increased in control group in comparison with sham group. Although cytokine levels in the study groups were moderately increased as compared with sham group, all of three groups had significantly reduced levels than control group. There were no significant differences between the study groups regarding the serum cytokine levels. CONCLUSION: These findings indicate that inflammation plays an essential role in skeletal muscle I/R injury. Our results suggested IPC and NAC exert beneficial effects on I/R induced inflammatory process in skeletal muscle. It was observed that there was no superiority of either of the measures over each other regarding the serum cytokine levels and concomitant use of them did not generate an additional benefit.

Keywords

Ischemia-reperfusion, ischemic preconditioning, N-acetylcysteine, cytokine

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