To Protect Fatty Livers from Ischemia Reperfusion Injury: Role of Ischemic Postconditioning

Abstract

Background The benefit of ischemic postconditioning (IPostC) might be the throttled inflow following cold ischemia. The current study investigated advantage and mechanisms of IPostC in healthy and fatty rat livers. Methods Male SD rats received a high-fat diet to induce fatty livers. Isolated liver perfusion was performed after 24 h ischemia at 4 °C as well as in vivo experiments after 90 min warm ischemia. The so-called follow-up perfusions served to investigate the hypothesis that medium from IPostC experiments is less harmful. Lactate dehydrogenase (LDH), transaminases, different cytokines, and gene expressions, respectively, were measured. Results Fatty livers showed histologically mild inflammation and moderate to severe fat storage. IPostC reduced LDH and TXB 2 in healthy and fatty livers and increased bile flow. LDH, TNF-α, and IL-6 levels in serum decreased after warm ischemia + IPostC. The gene expressions of Tnf, IL-6, Ccl2, and Ripk3 were downregulated in vivo after IPostC. Conclusions IPostC showed protective effects after ischemia in situ and in vivo in healthy and fatty livers. Restricted cyclic inflow was an important mechanism and further suggested involvement of necroptosis. IPostC represents a promising and easy intervention to improve outcomes after transplantation.

The Role of the JAK-STAT Signaling Pathway in the Protective Effects of Hepatic Ischemia Post-Conditioning against the Injury Induced by Ischemia/Reperfusion in the Rat Liver

“…Studies show that IPOC is able to reduce IR injuries in a variety of tissues including the lung, 14 kidney, 15 heart, 16 intestine, 17 brain, 18 and liver. 19 Goodman et al have shown that the protective effects of post-conditioning against IR injuries are mediated via activation of the JAK-STAT pathways in the isolated mouse heart. 20 However, there is not enough evidence to show the possible role of the JAK-STAT signaling pathway in the protective effects of IPOC against the hepatic injury induced by IR.…”