Prevention of TLR9 Pathway in Warm Ischemia in Porcine Donor Liver after Cardiac Death.

Objective: To investigate effect of warm ischemia after cardiac death on activation of TLR9 pathway in porcine liver. Methods: Donor of cardiac death (DCD) model was established with Duroc, Landrace, Large White crossbred pigs. Liver tissues from the animals were harvested at 0, 5, 10, 15, 25 and 30 minutes after warm ischemia for analysis of expression of TLR9, IRF7, IEN-beta, and INF-alpha at mRNA and protein levels by real-time PCR and western blot, respectively, and for assessment of NE-kappa B/DNA binding activity by western blot detection of p65 protein. Results: Ischemia induced TLR9, IRE7, IEN-beta, and TNF-alpha expression at both mRNA and protein levels in an ischemic time dependent manner. Among them, expression of INF-a and IFN-beta was induced later than TLR9 and IRF7 did. Ischemia also enhanced NF-kappa B binding to DNA in the DCD liver tissue. Pretreatment with iCpG specifically blocked activation of TLR9 pathway triggered by ischemia in liver and protected the animals from ischemia-caused liver tissue damage. Conclusion: Warm ischemia activates TLR9 pathways in the porcine liver tissue. Blocking TLR9 pathway could offer protection from ischemia-caused liver tissue in DCD liver transplantation. (C) 2017 The Author(s) Published by S. Karger AG, Basel