Safra yolu bağlanmış sıçanlarda antitrombotik ajan dalteparinin hepatik fibrozis gelişimini önlemedeki rolü
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Dosyalar
Tarih
2010
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Yayıncı
Trakya Üniversitesi Tıp Fakültesi
Erişim Hakkı
info:eu-repo/semantics/openAccess
Özet
Sirozda orta ve geniş portal ven ve hepatik ven trombozları sık görülür ve bu trombozlar parankimal tükenmeden tam bir siroza ilerleyişte önemli bir rol oynarlar. Bu çalışmada antitrombotik ajan dalteparinin hepatik fibrozis ve siroz gelişimi önlemedeki etkinliği incelenmiştir. Kırk adet Wistar-Albino cinsi erişkin sıçan çalışmaya dahil edilmiş; sağlıklı kontrol (n=10), sham (n=10), safra yolu ligasyonu (n=10) ve safra yolu ligasyonu+dalteparin (n=10) (50 IU/kg/gün intraperitoneal) olacak şekilde 4 gruba ayrılmıştır. Otuzbeşinci gün sonunda bütün sıçanlar sakrifiye edilmiştir. Karaciğerdeki vasküler trombozların varlığını tayin etmek ve dalteparinin etkinliğini saptamak için bütün hayvanların serumlarında D-dimer düzeyi, karaciğer dokularında ise immünhistokimyasal olarak fibrinojen boyama yapıldı. Işık mikroskobisi altında histopatolojik incelemede nekroinflamsyonun derecesi ve hepatik fibrozisin evresi değerlendirilmiştir. Karaciğerdeki hepatik fibrozisi saptamak ve dalteparinin etkinliğini değerlendirmek için biyokimyasal yöntemle doku hidroksiprolin tayini, immünhistokimyasal boyama ile alfa düz kas aktin, transforme edici büyüme faktörü beta reaktivitesi bakılmıştır. Otuzbeş günlük dalteparin tedavisi ile safra yolu bağlanmış sıçanlarda serum D-dimer düzeyinin düştüğü (p<0,05) ve karaciğer dokusu fibrinojen reaktivitesinin azaldığı (p<0,001) saptandı. Benzer şekilde 35. günün sonunda histopatolojik incelemede nekroinflamatuar aktivite derecesi ve fibrozis skorları azalmış (p<0,001) bulundu. İmmünhistokimyasal boyamada alfa düz kas aktin (p<0,0001) ve transforme edici büyüme faktörü beta (p<0,0001) reaktivitesi dalteparin tedavisi ile daha düşük bulundu. Biyokimyasal olarak bakılan doku hidroksiprolin düzeyleri dalteparin tedavisi ile azaldı (p<0,01). Sonuç olarak, safra yolu bağlı sıçanlarda dalteparin tedavisi karaciğer dokusunda tromboz, inflamasyon ve hepatik fibroz gelişimini engeller.
Abstract
Enlarged portal vein and hepatic vein thrombosis are common complications of cirrhosis and these thromboses play an important role in the development of complete cirrhosis before the failure of the paranchyme. In this study, the effects of an antithrombotic agent dalteparin on the prevention of hepatic fibrosis and the development of cirrhosis. Forty Wistar-Albino adult rats are enrolled in this study, and divided into four groups as healthy controls (n=10), sham (n=10), bile duct ligation (n=10) and bile duct ligation + dalteparin (50 IU/kg/day via intraperitoneal route) (n=10). At the end of thirthy-five days all rats have been sacrificed. Serum levels of D-dimer as well as immunohistochemical fibrinogen staining was performed in the liver tissue samples of all animals to determine the presence of vascular thrombosis in the liver and the effectivity of dalteparin. The degree of necro-inflammation and the grade of hepatic fibrosis were evaluated histopathologically with light microscobe. Tissue hydroxiproline with biochemical methods and ?-Smooth muscle actin, Transforming growth factor-ß reactivity with immunohistochemical methods were evaluated to determine the hepatic fibrosis and the effectivity of dalteparin. The serum levels of D-dimer (p<0,05) and the fibrinogen reactivity within the liver tissues (p<0,001) were observed to be decreased in the bile duct ligated animals after thirty-five days dalteparin treatment. Similarly, the degrees of the necroinflammatory activity and fibrosis scores were observed to be decreased (p<0,001) with the histopathological evaluation at the end of thirty-five days. With the immunohistochemical staining, the reactivities of ?-Smooth muscle actin (p<0,0001) and Transforming growth factor-ß (p<0,0001) were observed to be decreased with dalteparin treatment. The levels of tissue hydroxiproline determined with biochemical methods were also decreased with dalteparin treatment (p<0,01). As a result, dalteparin treatment prevents the development of thrombosis, inflammation and hepatic fibrosis in the liver tissues of bile duct ligated rats.
Abstract
Enlarged portal vein and hepatic vein thrombosis are common complications of cirrhosis and these thromboses play an important role in the development of complete cirrhosis before the failure of the paranchyme. In this study, the effects of an antithrombotic agent dalteparin on the prevention of hepatic fibrosis and the development of cirrhosis. Forty Wistar-Albino adult rats are enrolled in this study, and divided into four groups as healthy controls (n=10), sham (n=10), bile duct ligation (n=10) and bile duct ligation + dalteparin (50 IU/kg/day via intraperitoneal route) (n=10). At the end of thirthy-five days all rats have been sacrificed. Serum levels of D-dimer as well as immunohistochemical fibrinogen staining was performed in the liver tissue samples of all animals to determine the presence of vascular thrombosis in the liver and the effectivity of dalteparin. The degree of necro-inflammation and the grade of hepatic fibrosis were evaluated histopathologically with light microscobe. Tissue hydroxiproline with biochemical methods and ?-Smooth muscle actin, Transforming growth factor-ß reactivity with immunohistochemical methods were evaluated to determine the hepatic fibrosis and the effectivity of dalteparin. The serum levels of D-dimer (p<0,05) and the fibrinogen reactivity within the liver tissues (p<0,001) were observed to be decreased in the bile duct ligated animals after thirty-five days dalteparin treatment. Similarly, the degrees of the necroinflammatory activity and fibrosis scores were observed to be decreased (p<0,001) with the histopathological evaluation at the end of thirty-five days. With the immunohistochemical staining, the reactivities of ?-Smooth muscle actin (p<0,0001) and Transforming growth factor-ß (p<0,0001) were observed to be decreased with dalteparin treatment. The levels of tissue hydroxiproline determined with biochemical methods were also decreased with dalteparin treatment (p<0,01). As a result, dalteparin treatment prevents the development of thrombosis, inflammation and hepatic fibrosis in the liver tissues of bile duct ligated rats.
Açıklama
Tıpta Uzmanlık Tezi
Anahtar Kelimeler
Gastroenteroloji, Gastroenterology, Tıp Bilimleri, Teknoloji, Hastalıklar, Hepatik Fibrozis, Tromboz, Dalteparin
