Yağlı Karaciğer Modelinde Soğuk İskeminin Ampk Regülasyonu Üzerine Etkileri

Abstract

It has been observed that primary dysfunction and rejection problems are more common when fatty liver transplantation is performed. AMPK has organ protective functions during ischemia. Metformin has been used for the activation of AMPK in hepatocytes. In this study, it is examined the alteration of AMPK proteins in fatty and normal livers with or without metformin at varying times of ischemia. 7-week C7BL56 mice(n=110) were randomly divided into four groups; fatty and not-fat without metformin, fatty and non-fat with metformin.A diet model was administered for ten weeks for achieving fatty liver. 0.2 m/kg of metformin was administered by oral gavage for the last four weeks. After performing total hepatectomy, the tissues were kept for 0-6-12-24 hour ischemia periods with UW solutions. Histopathological examinations were performed to calculate scores of macrosteatosis, fibrosis, inflammation, vacuolar changes, necrosis. Western blot method used for p-AMPK and AMPK protein expressions. Descriptive statistics performed. It was shown statistically that fatty liver decreased with metformin (%68 ± 24 vs %47 ±25; p <0,001). Fatty liver groups had more seve necroinflammatory focus and pericentral inflammation than non-fat groups. Both findings were reduced by metformin. There was significantly less evidence of necrosis in all liver groups with metformin . (%7,4 vs %43,5; p <0,001). It was shown that fatty liver had a lower and later AMPK response than non-fat livers, and this difference was corrected with metformin. AMPK plays an important role in the ischemia response of the liver, and it is possible that metformin can increase the resistance of the fatty liver to ischemia and the success of transplantation.