Karaciğer iskemi- reperfüzyon hasarının engellenmesinde sitidin-5'-difosfat kolin,oktreotid ve enoksaparin sodyum'un biyokimyasal ve histopatolojik etkileri
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Date
2008
Authors
Şen, Gürol
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Publisher
Uludağ Üniversitesi
Abstract
İskemi- reperfüzyon hasarı karaciğer , transplantasyon cerrahisinin önemli morbidite ve mortalite nedenidir. Bu hasarı önlemede birçok ajan kullanılmış ve halen kullanılmaktadır. Bu çalışmada karaciğer iskemi-reperfüzyon hasarının engellenmesinde sitidin-5'-difosfat kolin (CDP-C), oktreotid (OC) ve enoksaparin (ENP) sodyum'un biyokimyasal ve histopatolojik etkileri araştırılmıştır.Çalışmada 72 adet dişi `'wistar albino'' rat kullanıldı. 12' şer denekli 6 gruptan grup A' ya (sham) sadece laparatomi uygulandı. B grubuna laparatomi'yi takiben 30 dk hepatik iskemi ve 2 saat reperfüzyon uygulandı. C grubuna standart iskemi reperfüzyon sürecinden 2 saat önce 600 µmol / kg intraperitoneal CDP-C; D grubuna standart iskemi reperfüzyon sürecinden 24 saat ve 2 saat önce 25 µg / kg subkutan OC, E grubuna yine standart iskemi reperfüzyon sürecinden 24 saat ve 2 saat önce 1,5 mg / kg subkutan ENP, F grubuna standart iskemi reperfüzyon sürecinden 24 saat ve 2 saat once, 25 µg / kg subkutan OC ve 1,5 mg / kg subkutan ENP kombine uygulandı. Reperfüzyon sonunda karaciğer fonksiyonlarını değerlendirmek için serumda aspartat aminotransferaz (AST), alanin aminotransferaz (ALT), laktat dehidrogenaz (LDH) ve ?-glutamil transferaza (?-GT) bakıldı. İskemi- reperfüzyon hasarı başta olmak üzere genel inflamatuvar yanıtı yansıtan proinflamatuvar bir sitokin olan TNF- ? alınan serum örneklerinde ölçüldü. Ratların karaciğerlerinden alınan doku örneklerindeki patolojik değişiklikler incelendi.CDP-C uygulanan grupta AST, ALT, LDH ve ?-GT seviyeleri en yüksek bulundu. Özellikle OC grubunda tüm değerler I/R grubuna göre anlamlı olarak düşük (p<0,001) bulundu.Bu grupta hepatik nekroza da rastlanmadı.Karaciğer I/R hasarında hücresel değişikliklerin stabilize edilmesi ve inflamasyonun baskılanmasında OC'nin tek başına uygulanması CDP-C, ENP ve OC+ENP kombinasyonundan anlamlı olarak etkin bulundu. CDP-C ve ENP'nin belirgin etkinlikleri görülmedi.
The ischemia-reperfusion (I/R) injury is an important cause of mortality and morbidity in liver transplantation surgery. There have been various therapeutic agents used to prevent this injury. In this study the biochemical and histopathologic influences of cytidine-5'-diphosphate choline (CDP-C), octreotide (OC) and enoxaparin sodium (ENP) on prevention of hepatic ischemia-reperfusion injury were investigated .72 female w.a. rats were used in this study.The animals were randomly divided into six groups.In the first group (Sham, group A), only laparatomy was performed. Second group (I/R group, group B) was subjected to 30 min of hepatic ischemia and 2 hours of reperfusion. İn group C (CDP-C group), 600 µmol/kg CDP-C was administered intraperitoneally,2 hours before ischemia-reperfusion period. In D, E, and F groups, octreotid (OC) 25µg/kg; enoxaparin sodium (ENP) 1,5 mg/kg, and OC+ENP combination(respectively) administrated subcutaneously 24 h and 2 h before I/R injury respectively. Serum aspartat amino transpherase (AST), alanine amino transpherase (ALT), lactate dehidrogenase (LDH) and γ-glutamyl transpherase (γ-GT) levels were measured to evaluate the liver damage after reperfusion. A proinflammatory cytokine; serum TNF-α levels were also used as a marker of inflammatory response. The histopathological examination was performed on the tissue samples of rats' livers. The AST, ALT, LDH and γ-GT levels were found to be highest in the group C (CDP-C group) except group B. All parameters in OC group were significantly lower than the other medicated groups, and also there was not hepatic necrosis (p<0.001) .Conclusion; OC administration is significantly more effective than CDP-C, ENP or ENP+OC combination against liver I/R injury.
The ischemia-reperfusion (I/R) injury is an important cause of mortality and morbidity in liver transplantation surgery. There have been various therapeutic agents used to prevent this injury. In this study the biochemical and histopathologic influences of cytidine-5'-diphosphate choline (CDP-C), octreotide (OC) and enoxaparin sodium (ENP) on prevention of hepatic ischemia-reperfusion injury were investigated .72 female w.a. rats were used in this study.The animals were randomly divided into six groups.In the first group (Sham, group A), only laparatomy was performed. Second group (I/R group, group B) was subjected to 30 min of hepatic ischemia and 2 hours of reperfusion. İn group C (CDP-C group), 600 µmol/kg CDP-C was administered intraperitoneally,2 hours before ischemia-reperfusion period. In D, E, and F groups, octreotid (OC) 25µg/kg; enoxaparin sodium (ENP) 1,5 mg/kg, and OC+ENP combination(respectively) administrated subcutaneously 24 h and 2 h before I/R injury respectively. Serum aspartat amino transpherase (AST), alanine amino transpherase (ALT), lactate dehidrogenase (LDH) and γ-glutamyl transpherase (γ-GT) levels were measured to evaluate the liver damage after reperfusion. A proinflammatory cytokine; serum TNF-α levels were also used as a marker of inflammatory response. The histopathological examination was performed on the tissue samples of rats' livers. The AST, ALT, LDH and γ-GT levels were found to be highest in the group C (CDP-C group) except group B. All parameters in OC group were significantly lower than the other medicated groups, and also there was not hepatic necrosis (p<0.001) .Conclusion; OC administration is significantly more effective than CDP-C, ENP or ENP+OC combination against liver I/R injury.
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Keywords
Karaciğer, İskemi-reperfüzyon, Sitidin-5'-difosfat kolin, Oktreotid, Enoksaparin sodyum, Liver, Ischemia-reperfusion, Citydin-5’diphosphate colin, Octreotide, Enoksaparine sodium
Citation
Şen, G. (2008). Karaciğer iskemi- reperfüzyon hasarının engellenmesinde Sitidin-5'-Difosfat Kolin,Oktreotid ve Enoksaparin Sodyum'un biyokimyasal ve histopatolojik etkileri. Yayınlanmamış uzmanlık tezi. Uludağ Üniversitesi Tıp Fakültesi.