YAŞLANMA SÜRECİ
6. SONUÇ ve ÖNERİLER
Bu deneysel çalışmada rat karaciğer iskemi-reperfüzyon modelinde, 10 µg/kg ve 100 µg/kg deksmedetomidinin iskemik karaciğer hasarı üzerine etkileri, MDA, SOD, KAT, GSH, GSH-Px ile değerlendirilmiştir.
Karaciğer İR hasarı oksidatif strese neden olur. MDA düzeyini artar; SOD, KAT, GSH ve GSH-Px enzim aktivitelerini azaltır.
Çalışmamızda deksmedetomidinin her iki dozu da İR hasarını azaltmakla birlikte 100 µg/kg’lik dozu daha etkindir.
Karaciğer İR hasarının klinik tedavisinde deksmedetomidin uygulaması karaciğer hasarını azaltabilir.
Deksmedetomidinin karaciğer İR hasarına karşı koruyucu etki mekanizmalarının açığa çıkarılması için ileri çalışmaların yapılması uygun olacaktır.
7. ÖZET
Amaç: Karaciğer İR hasarı hepatik doku ve hücrelerde bir seri hasara sebep olabilir. Bu da hastaların prognozunu, operasyonun başarısını etkileyen temel faktörlerden biridir. Karaciğer nakli sonrası kötü fonksiyon gören greftin yaygın görülen bir sebebidir. İskemi-reperfüzyon hasarının mekanizması tam olarak açıklanamamıştır ancak kanıtlar hasarda anahtar rolün serbest oksijen radikalleri olduğuna işaret etmektedir.
Deksmedetomidin çok güçlü ve ileri derecede selektif bir α2 reseptör agonistidir. Artan klinik kullanımına karşın karaciğer iskemi reperfüzyon hasarına karşı deksmedetomidinin etkileri bilinmemektedir.
Çalışmamızda ratlarda, karaciğer İR ile oluşturulan oksidatif hasara karşı deksmedetomidinin koruyucu etkisi olup olmadığını inceledik.
Gereç ve Yöntem: Çalışmada 40 adet ağırlıkları 250-350 g arasında değişen Sprague-Dawley genç, erkek rat randomize olarak 10’arlı 4 gruba ayrıldı.
Grup 1: Batın açıldı ancak oklüzyon uygulanmadı.
Grup 2: Batın açıldıktan sonra segmental hepatik iskemi modeli ile 60 dakika iskemi ve 60 dakika reperfüzyon uygulandı.
Grup 3: İskemiden 30 dakika önce deksmedetomidin 10 µg/kg periton içine (ip) uygulandı.
Grup 4: İskemiden 30 dakika önce deksmedetomidin 100 µg/kg i.p uygulandı. Deney tamamlandıktan sonra ratlar kalpten kanatılarak sakrifiye edildi. Çıkarılan karaciğer dokuları alüminyum folyoya sarılarak biyokimyasal analizler
Bulgular: Doku MDA düzeyi Grup 1’e göre Grup 2’de anlamlı yüksek idi (p<0.05). Grup 2’ye göre Grup 3 ve 4’te MDA düzeylerinde ki düşüş anlamlı idi (p<0.05).
Doku SOD ve KAT düzeyleri Grup 1’e göre Grup 2’de anlamlı düşük bulundu (p<0.05). Grup 2’ye göre Grup 4’de anlamlı artış olduğu görüldü (p<0.05).
Karaciğer dokusundaki GSH düzeyi Grup 1’e göre Grup 2’de anlamlı düşük bulundu (p<0.05). Grup 2’ye göre Grup 3 ve 4’de GSH düzeylerinde anlamlı artış saptandı (p<0.05).
Doku GSH-Px düzeyi Grup 1’e göre Grup 2 ve Grup 3’de anlamlı düşük bulundu (p<0.05). Grup 3 ve 4 arasında da GSH-Px aktivitesi açısından anlamlı fark vardı (p<0.05).
Sonuç: Ratlarda yapılan deneysel karaciğer İR modelinde deksmedetomidinin doza bağlı olarak karaciğer oksidatif hasarını azalttığı görülmüştür. Araştırmamızın sonuçları, deksmedetomidinin karaciğer iskemi- reperfüzyon hasarındaki muhtemel koruyucu rolünün daha geniş deneysel ve klinik çalışmalarla desteklenmesi gerektiği kanaatini doğurmuştur.
Anahtar Kelimeler: Karaciğer, iskemi-reperfüzyon, hasar, deksmedetomidin.
8. SUMMARY
Aim: The IR injury of liver may cause a series of damage to hepatic tissue and cells. It is one of the factors which can affect the prognosis of the patients and the success of the operation. The IR injury of liver is a frequent cause of poor graft function in the postoperative period. The mechanism of the ischemia-reperfusion injury has not been fully explained; however, the evidence shows that free oxygen radicals have the key role in the injury.
Dexmedetomidine is a very strong and a highly selective α2 receptor agonist. Its effects against the reperfusion injury have not known despite increasing clinical use of this agent.
The aim of this study was to evaluate the protective effects of dexmedetomidine against oxidative injury resulted from liver IR in rats.
Materials and Methods: 40 Sprague-Dawley young, male rats weighing between 250 and 350 g were randomly separated into four groups, including 10 in the each group.
Group 1: The abdomen was opened but hepatic portal occlusion wasn’t applied. Group 2: After the abdomen was opened, 60 minutes ischemia and 60 minutes reperfusion were applied through segmental hepatic ischemia model.
Group 3: 30 minutes before the ischemia, dexmedetomidine 10 µg/kg was applied into peritoneal cavity.
Group 4: 30 minutes before the ischemia, dexmedetomidine 100 µg/kg was applied into peritoneal cavity.
After the experiment was completed, the rats were sacrificed by making them bleed. The extracted livers were kept in the deep-freezer in -80 ◦C by wrapping them in an aluminum foil.
Results: Tissue MDA level was significantly high in Group 2 than Group 1 (p<0.05). The decrease in Groups 3 and 4 was significant than Group 2 (p<0.05).
Tissue SOD and KAT levels was detected low in Group 2 than Group 1 (p<0.05). There was a significant increase in Group 4 than Group 2 (p<0.05).
The GSH level in the liver tissue was significantly lower in Group 2 than when compared with Group 1 (p<0.05). There was a significant increase in GSH levels in Groups 3 and 4 than Group 2 (p<0.05).
Tissue GSH-Px level was detected significantly low in Groups 2 and 3 when compared with Group 1 (p<0.05). There was a significant difference between Group 3 and 4 in the terms of GSH-Px activity (p<0.05).
Conclusion: In the liver ischemia reperfusion model carried out in the rats, it was concluded that dexmedetomidine was decreased the liver oxidation depending on the dose. The results of this study indicate the potential role of the dexmedetomidine in the protection of reperfusion damage of the liver ischemia and this must be supported by means of detailed experimental and clinical studies.
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