生长激素释放肽对失血性休克大鼠心肌保护作用及对核因子-κB的影响  

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

作　　者：张丽娜 岳子勇 Zhang Li-na;Yue Zi-yong(Department of Anesthesiology,the Fourth Affiliated Hospital of Harbin Medical University,Harbin 150001,China)

机构地区：[1]哈尔滨医科大学附属第四医院麻醉科,黑龙江哈尔滨150001

出　　处：《中国急救医学》2019年第1期66-70,共5页Chinese Journal of Critical Care Medicine

基　　金：国家自然科学基金项目(30772085).

摘　　要：目的观察生长激素释放肽(ghrelin)对失血性休克(hemorrhagic shock,HS)大鼠心肌的保护作用及对核因子-κB(NF-κB)表达的影响。方法32只成年雄性SD大鼠随机分为四组:假手术组(sham)、假手术+ghrelin组(sham+ghrelin)、HS组、HS+ghrelin组,每组8只。经大鼠股动脉放血使平均动脉压(MAP)维持在40 mm Hg左右1 h,然后静脉给予10 nmol/kg的ghrelin或等量生理盐水注射,随后立即用大鼠自体血和等量乳酸林格液复苏并观察2 h,同时进行血流动力学监测。复苏结束后,采集心肌组织行病理学检查;检测心肌丙二醛(MDA)、超氧化物歧化酶(SOD)活性及髓过氧化物酶(MPO)活性;取大鼠血浆测定肿瘤坏死因子-α(TNF-α)和白细胞介素-6(IL-6)水平;取心肌组织测定NF-κB蛋白的表达。结果在复苏后相同时间点,HS组大鼠MAP较sham组显著降低(P﹤0.05),ghrelin处理后能够显著缓解HS大鼠复苏后的MAP降低程度(P﹤0.05);与sham组比较,HS组大鼠心肌损伤程度、MDA含量、MPO活性、血浆炎症因子表达以及NF-κB蛋白表达显著增高,SOD活性显著降低(P﹤0.05);与HS组比较,HS+ghrelin组心肌损伤程度、MDA含量、MPO活性、血浆炎症因子表达以及NF-κB蛋白表达显著降低[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活性显著增强[(72.77±4.90)U/mg prot vs.(89.31±7.35)U/mg prot,P﹤0.05]。结论Ghrelin对HS大鼠心肌有保护作用,这种保护机制与抑制NF-κB信号通路的表达有关。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-αand 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-αand 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-a:(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-kB signaling pathway.

关 键 词：失血性休克(HS) 心肌保护 生长激素释放肽(ghrelin) 核转录因子-kB(NF-κB) 

分 类 号：R459.7[医药卫生—急诊医学]