Effect of exogenous ghrelin on myocardial protection and NF - κB in rats after hemorrhagic shock

Zhang Li-na; Yue Zi-yong

doi:10.3969/j.issn.1002-1949.2019.01.014

Abstract：Objective To investigate the effect and the underlying mechanism of exogenous ghrelin on myocardial protection in rats after hemorrhagic shock ( HS). Methods Thirty two male Sprague-Dawley ( SD) rats weighing 300 ~350 g were randomly divided into four groups ( n=8 per group): sham operation group ( sham group ), sham operation plus ghrelin group ( sham + ghrelin group), HS group, HS plus ghrelin group ( HS+ghrelin group). HS was induced in male SD rats by withdrawing blood to a mean arterial pressure ( MAP) of 40 mm Hg for 1 h, rats were then received ghrelin (10 nmol/kg) or vehicle intravenously and resuscitated with the shed blood and equal Ringer Lactate solution followed by an observation for 2 h, with blood gas analysis and hemodynamic monitoring. After resuscitation, samples were collected and analyzed for myocardial histopathology, malondialdehyde (MDA) content, superoxide dismutase(SOD) activity, myeloperoxidase ( MPO) activity, and plasma inflammatory cytokines ( TNF -α and IL -6), expression of nuclear NF -κB were also evaluated. Results Ghrelin alleviated decreased MAP after resuscitation compared with HS rats at both time points following resuscitation ( P <0. 05). Compared with the two sham groups, myocardial injury, MDA content, MPO activity, plasma TNF - α and IL -6 levels, NF - κB activation from HS rats were significantly increased and SOD activity was lower than sham group(P<0. 05). After administration of ghrelin, those parameters analyzed were lower than those without ghrelin in HS rats[[MDA:(2. 86 ± 0. 08)nmol/mg prot vs. (1. 45 ± 0. 29)nmol/mg prot,MPO:(2. 23 ± 0. 20)U/g prot vs. (1. 87 ± 0. 22) U/g prot, TNF-α:(62. 71 ± 4. 31) pg/mL vs. (35. 16 ± 4. 06) pg/mL, IL-6:(73. 33 ± 13. 94) pg/mL vs. (42. 22 ± 7. 92) pg/mL, P<0. 05]; SOD activity of HS+ghrelin group was significantly higher than that of HS group[(72. 77 ± 4. 90)U/mg prot vs. (89. 31 ± 7. 35)U/mg prot, P<0. 05]. Conclusion Exogenous ghrelin attenuates myocardial injury after hemorrhagic shock, and these beneficial effects of ghrelin appear to be mediated through inhibition the NF-κB signaling pathway.