Sustained Isoprostane E2 Elevation, Inflammation and Fibrosis after Acute Ischaemia-Reperfusion Injury Are Reduced by Pregnane X Receptor Activation

摘要: Liver grafts donated after cardiac death are increasingly used to expand the donor pool but prone ischaemic-type biliary lesions. The anti-inflammatory effects of activated pregnane X receptor have previously been shown be beneficial in a number inflammatory liver conditions. However, its role reducing peri-portal inflammation and fibrosis following ischaemia-reperfusion injury has not investigated. Hepatic response activation was examined partial hepatic induced by surgically clamping left middle lobar blood vessels rats. Molecular pathological changes were over 28 days. Ischaemia-reperfusion resulted transient cholestasis associated with microvillar epithelial cell membranes hepatocellular which resolved within days reperfusion. contrast chemically-induced acute injuries, this followed sustained elevation isoprostane E2, that remained unresolved ischaemic reperfused lobe for at least clamping. Administration pregnenolone-16α-carbonitrile--a rodent-specific activator--resulted significant reductions cholestasis, injury, E2 levels, fibrosis. therefore results fibrotic persist well beyond initial insult. Drug-mediated reduced these adverse rats, suggesting is viable drug target reduce lesions recipients transplants death.