Protective effect of peroxisome proliferator-activated receptor γ agonist 15d-PGJ2 against reperfusion injuryin small-for-size rat liver grafts

Abstract

Objective To investigate the protective effect of peroxisome proliferator-activated receptor γ (PPARγ) agonist 15d-PGJ2 against reperfusion injury in small-for-size liver grafts and its probable mechanisms. Methods 108 adult male SD rats were randomly divided into three groups: ( 1 ) 15d-PGJ2 group; (2) 15d-PGJ2 + GW9662 group; (3) NS control group. Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels at 6, 24 and 72 h after reperfusion and histopathological changes were analyzed, the contents of malondialdehyde (MDA) and superoxide dismutase (SOD) in liver grafts after 24 h were determined, myeloperoxidase (MPO) activity was examined to assay neutrophil infiltration into the grafts at 24 h after reperfusion, and transforming growth factor (TGF)-α levels at 24 h after reperfusion were measured by using enzyme-linked immunosorbent assay ( ELISA method). Results As compared with NS control group and 15d-PGJ2 + GW9662 group, serum AST and ALT levels were significantly reduced at 6, 24 and 72 h after reperfusion in 15d-PGJ2 group (P ＜0. 01 ). Histopathological analysis revealed apparent bulb-like degeneration, hepatic sinusoid dilation, and inflammatory cell infiltration in periportal area at 24 h in NS group and 15d-PGJ2 + GW9662 group after transplantation, while in the 15d-PGJ2 group, minimal damage was observed at 24 h after transplantation under the light microscopy, the contents of MDA were lower and SOD levels were higher than in other groups ( P ＜0. 01 ). As compared with NS group and 15d-PGJ2 + GW9662 group, TNF-α levels and MPO activity at 24 h after transplantation were also significantly decreased in 15d-PGJ2 group (P ＜ 0. 01 ). Conclusion PPARγagonist 15d-PGJ2 could ameliorate reperfusion injury in small-for-size liver grafts significantly, which was mediated in part by increasing antioxidant ability, inhibiting lipid peroxidation, and down-regulating inflammatory reaetion. Key words: PPARγ; Liver transplantation; Repeffusion injury