İlkay Güler1, Alper Akcan1, Engin Ok1, Hülya Akgün2, Sebahattin Muhtaroğlu3, Namık Yılmaz1

1Erciyes Üniversitesi Tıp Fakültesi Genel Cerahi AD, KAYSERİ
2Erciyes Üniversitesi Tıp Fakültesi Patoloji AD, KAYSERİ
3Erciyes Üniversitesi Tıp Fakültesi Biyokimya AD, KAYSERİ


Purpose: The aim of the study is to investigate the effects of Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF) on ischemia-reperfusion induced apoptosis and hepatic regeneration in a partially hepatectomized rat model.

Materials and Methods: Fifty rats were used and they were divided into five groups, each including ten rats. A juguler vein catheter placed to all except sham group and normal saline infusion was started 1 hour before operation. A midline laparotomy performed. Sham group rats were sacrified after portal dissection. Total ischemia performed to the other groups, after 70% hepatectomy the occlusion opened for reperfusion of the remnant liver. Before the operation (60 min.) 0.02 ml normal saline was given to control groups and 1 μg/kg GM-CSF was given to study groups subcutaneously administered. Blood samples were collected from v cava inferior for AST, ALT, LDH and sFas levels at the 2nd and 48th hours of reperfusion with performing relaparotomy. Remaining liver tissues were resected and weigthed. Relative liver mass, malondialdehyde (MDA), mitotic index and Fas immunohistochemical (IHC) staining evaluations from tissue samples were performed.

Results: Mitotic index and relative liver weigths at GM-CSF group were significantly higher at 48th hour (p<0.05). AST,ALT ve LDH levels were increased at 2nd hour. However these levels were decreased in the study group at the 48th hour. Hepatic MDA level was high at 2nd but lower at 48th hour than other groups. sFas level and Fas IHC stainings were similar. But they were lower at 2nd and 48th hours in the GM-CSF group (p<0.05). Ischemia-reperfusion injury was high at 2nd hour and but there was no difference between saline and GM-CSF groups. However the injury decreased significantly at 48th hour, at the study group.

Conclusions: GM-CSF, increases liver regeneration both morphologically and functionally after Pringle maneuver and partial hepatic resection. This application also decreases apoptosis and ischemia-reperfusion injury at the advanced stages of reperfusion.

Keywords: Ischemia-reperfusion, hepatic resection, apoptosis, Fas, GM-CSF