Ghrelin May Inhibit Inflammatory Response and Apoptosis During Ischemia-Reperfusion Injury

Background. Ghrelin, a novel growth hormone-releasing peptide, has both anti-inflammatory and anti-apoptotic effects on human endothelial cells. We evaluated the protective effects of ghrelin against ischemia-reperfusion injury (IRI) in a murine heterotopic cervical heart transplan-tation model. Methods. Donor hearts from C57BL/6J wild-type mice, which were kept in cold saline for 60 minutes, were heterotopically transplanted into C57BL/6J wild-type recipients. A day prior to heterotopic cervical heart transplantation, donor animals received either ghrelin (300 nmol/kg) or saline (0.3 mL) intraperitoneally. Upon reperfusion and postoperative day 1, ghrelin or saline was administered to the recipients. Donor hearts were procured on day 2. Results. Ghrelin injection did not result in any adverse effects in donors or recipients. Termi-nal deoxynucleotidyl transferase-mediated dUTP nick end labeling-positive cells were signifi- cantly decreased in the ghrelin group (0.38% +/- 0.21% vs 5.74% +/- 3.68%; P < .001). Both cleaved caspase-3 activity and Bcl-2/Bax ratio from the ghrelin group were significantly reduced compared to those in the control. Furthermore, the phosphorylated Akt/Akt ratio was higher in the ghrelin group (0.44 +/- 0.21 vs 0.14 +/- 0.03; P = .043). Nuclear factor-kappa B p65 nuclear translocation was reduced in the ghrelin hearts compared to the controls (3.17% +/- 1.84% vs 19.28% +/- 13.14%; P = .009). Vascular cell adhesion molecule-1, intracellular adhesion mole-cule-1, nuclear factor-kappa B, and tumor necrosis factor alpha levels were also significantly reduced in the ghrelin-treated group. No significant difference was observed in 8-isoprostane production between groups. Conclusion. Ghrelin inhibits the inflammatory response and apoptosis during transplant -related IRI. This study demonstrates the protective effects of ghrelin against IRI.