Current Topics in TransplantationExperimental studiesIRAK-4-shRNA Prevents Ischemia/Reperfusion Injury Via Different Perfusion Periods Through the Portal Vein After Liver Transplantation in Rat

•Interleukin-1 receptor-associated kinase-4 activity was suppressed by short hairpin RNA targeting interleukin-1 receptor-associated kinase-4 (IRAK-4-shRNA) through portal vein perfusion.•Perfusion of IRAK-4-shRNA during the cold ischemia period was more effective.•IRAK-4-shRNA prevented ischemia/reperfusion injury after liver transplantation.

BackgroundThis study analyzed the effects of short hairpin RNA targeting interleukin-1 receptor-associated kinase-4 (IRAK-4-shRNA) via portal vein perfusion during different periods on ischemia/reperfusion injury after liver transplantation.MethodsRats were randomly divided into 3 groups: the cold ischemia transfection group (CIT group, n = 18), in which graft livers were perfused with the plasmid of pSIIRAK-4 expressing IRAK-4-shRNA for 4 minutes (0.5 mL/min) via the portal vein during the cold ischemia period; the in vivo transfection group (IVT group, n = 18), in which equivalent volumes (2 mL) of IRAK-4-ShRNA plasmid (pSIIRAK-4) were injected during the operation; and the control group (n = 18), in which the rats received equivalent volumes of blank plasmid. At 0, 60, and 180 minutes after portal vein reperfusion, blood and liver tissues were collected for examination. IRAK-4 expression, nuclear factor kB (NF-kB) activity, tumor necrosis factor α, interleukin (IL)-1β, and IL-6 serum levels, as well as histologic changes, were detected.ResultsAt 0 minutes after reperfusion, IRAK-4 expression, NF-κB activity, and serum levels of tumor necrosis factor α, IL-1β, and IL-6 showed no significant differences among the 3 groups (P > .05). At 60 and 180 minutes after reperfusion, all indices of the IVT and control groups were significantly higher than those of the CIT group (P < .01). Meanwhile, all indices of the CIT group showed no significant differences at various time points (P > .05). Liver function and histologic changes exhibited less liver injury in the CIT group than in the other groups.ConclusionsIRAK-4 activity was suppressed by IRAK-4-shRNA through portal vein perfusion during the cold ischemia period, and IRAK-4-shRNA effectively prevented ischemia/reperfusion injury after liver transplantation.