Limb remote ischemic preconditioning attenuates liver ischemia reperfusion injury by activating autophagy via modulating PPAR-γ pathway

Abstract

To investigate the effect of limb remote ischemic preconditioning (RIPC) on hepatic ischemia/reperfusion (IR) injury and the underlying mechanisms. Rats were subjected to partial hepatic IR (60 min ischemia followed by 24 hours reperfusion) with or without RIPC, which was achieved by 3 cycles of 10 min-occlusion and 10 min- reperfusion at the bilateral femoral arteries interval 30 min before ischemia. Some rats were treated with a new PPAR-γ inhibitor, T0070907, before RIPC. At the end of reperfusion, liver injury was significantly increased (increases in Suzike's injury score, AST and ALT release), concomitant with elevated oxidative stress (increases in MDA formation, MPO activity, as well as the decrease in SOD activity) and inflammation (increases in TNF-α and IL-6 levels, decrease in IL-10 content). RIPC improved liver function and reduced histologic damage, accompanied by the increased PPAR-γ activation and autophagosome formation as well as the reduced autophagosome clearance. The beneficial effects of RIPC were markedly attenuated by T0070907, an inhibitor of PPAR-γ. RIPC exerts the protective effects on liver by activation of autophagy via PPAR-γ.