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Effect of exogenous ghrelin on myocardial protection and NF-κB in rats after hemorrhagic shock |
Zhang Li-na, Yue Zi-yong |
Department of Anesthesiology, the Fourth Affiliated Hospital of Harbin Medical University, Harbin 150001, China |
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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.
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Corresponding Authors:
Yue Zi-yong, E-mail: yueziyong@126.com
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