Anti-apoptotic Actions And Mechanisms Of Ghrelin In Cardiomyocytes After Hypoxia/Reoxygenation Injury

Objective—Ghrelin , a novel cardiovascular peptid derived mainly from gastrointestinal tract has cardiomyocyte protection effect against ischemia/reperfusion injury when administrated parenterally. However, the detail mechanisms through which Ghrelin exerts protection have not been determined . In this study , we try to explore the anti-apoptostic effect of Ghrelin in cardiomyocytes after Hypoxia/Reoxygenation injury and manifest the specific cellular singaling transduction pathway.Methods—Newborn SD rats' hearts were isolated and cardiomyocytes were separated by trypsin digestion method .The primary cardiomyocytes were collected and incubated in vitro and randomly alloted to 4 groups (1 .Control; 2. H/R group ; 3. H/R +Ghrelin group ; 4. H/R +Ghrelin +Wortmannin group) after 5 days of cultivation . Hypoxia/Reoxygenation injury was established by 4 hours of hyopxia and subsquently 1 hour of reoxygenation. Lactic dehydrogenase concentration , cell apoptotic rate and the expression ofphosph- Akt were detected by Automatic Biochemistry Analytic Instrument, Tunel method and Western blotting method respectively .Results — Compared with H/R group and H/R + Ghrelin + Wortmannin group , the LDH concentration in media was significantly reduced and the myocardium apoptotic rate was pretty low in H/R+Ghrelin group . Ghrelin also increased phosph- Akt activity but this effect was abolished by applying Wortmannin simultaneously.Conclusions — Ghrelin provides concrete protection against Hypoxia/Reoxygenation injury in the primary cultivated rat cardiomyocytes , which manifest dereasing LDH leaking , inhibitting cell apoptosis . The antiapoptotic effect is partly mediated by the activation of the PI3K /Akt ( Phosphatidylinositol-3 kinase/ Akt) pathway .