The Role of Macrophage Migration Inhibitory Factor in Remote Ischemic Conditioning Induced Hepatoprotection in a Rodent Model of Liver Transplantation.

Abstract

BACKGROUND:

Macrophage migration inhibitory factor (MIF) is an important stress-regulating mediator of acute ischemia/reperfusion (I/R) injury and ischemic conditioning. The present study aimed to investigate whether MIF is involved in the effects of remote ischemic conditioning (RIC) in a rat model of orthotopic liver transplantation (OLT).

METHODS:

OLTs were performed in male Lewis rats (245 g-340 g). Recipients were allocated in a randomized fashion into three experimental groups: remote preconditioning-RIPC, remote post-conditioning-RIPOST, control. RIC was applied as 4×5-5 min I/R via clamping of the infrarenal aorta. Animals were followed for 1, 3, 24, 168 h post-reperfusion (n = 6 recipient/group/time point). Graft micro- and macrocirculation and hepatocellular damage were assessed. Messenger ribonucleic acid (mRNA) expression, serum, and tissue protein levels of MIF, as well as additional markers of I/R injury, were measured.

RESULTS:

RIC resulted in a prominent downregulation of MIF mRNA, serum, and tissue protein. Compared with control, hepatocellular damage was significantly mitigated after RIPC or RIPOST (serum ALT; RIPC, RIPOST vs. Control, P = 0.008, P = 0.030, respectively). Graft circulation was better preserved in the RIC groups. Furthermore, there was a significant positive correlation between serum MIF and transaminase levels (r = 0.330; P = 0.02). RIC showed a significant effect on iNOS and STAT5 mRNA expressions. Supporting findings were obtained from the measurements of tissue CXCL12 mRNA expression and pAkt/Akt, pErk/Erk.

CONCLUSION:

In this sophisticated experimental model of OLT, RIC-induced hepatoprotective effects were associated with a downregulation of MIF at mRNA and protein levels, suggesting the role of MIF as a mediator in RIC-induced protection following OLT.

• Authors: Christoph Emontzpohl, Christian Stoppe, Alexander Theißen, Christian Beckers, Ulf P Neumann, Georg Lurje, Cynthia Ju, Jürgen Bernhagen, René H Tolba, Zoltan Czigany
• Journal: Shock (Augusta, Ga.) (Shock) Vol. 52 Issue 5 Pg. e124-e134 (11 2019) ISSN: 1540-0514 [Electronic] United States
• PMID: 30601408 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Macrophage Migration-Inhibitory Factors
• Intramolecular Oxidoreductases
• Mif protein, rat

Topics

• Animals
• Intramolecular Oxidoreductases (metabolism)
• Ischemic Preconditioning
• Liver (metabolism, pathology)
• Liver Transplantation
• Macrophage Migration-Inhibitory Factors (metabolism)
• Male
• Rats
• Rats, Inbred Lew