艾司洛尔对脓毒症大鼠心肌细胞线粒体膜电位及心肌组织NF-κB表达的影响

Effects of esmolol on mitochondrial membrane potential and expression of NF-κB in myocardial tissue of septic rats

目的探讨艾司洛尔对脓毒症大鼠心肌细胞线粒体膜电位及心肌组织核因子kappa-B(NF-κB)表达的影响。方法清洁级SD(SpragueDawley)大鼠100只,鼠龄6~8周,体质量110~150g,平均体质量130.65g。按随机数字表法分成5组,即对照组、模型组和艾司洛尔低剂量组(5.0mg/kg)、中剂量组(10.0mg/kg)、高剂量组(20.0mg/kg)。模型组、艾司洛尔各剂量组构建脓毒症模型,并于造模成功开始给予相应药物灌胃,对照组和模型组给予等体积0.9%氯化钠溶液(生理盐水)。实验结束后,检测大鼠心功能指标、大鼠心肌细胞凋亡水平、心肌细胞线粒体膜电位、NF-κB蛋白、mRNA水平、白细胞介素(IL)-2、IL-6、肿瘤坏死因子-α(TNF-α)蛋白水平。结果与模型组比较,艾司洛尔各剂量组心肌细胞凋亡指数、肌酸激酶(CK)、乳酸脱氢酶(LDH)、心肌组织NF-κBmRNA、蛋白表达水平、TNF-α、IL-2、IL-6表达水平降低,左心室收缩压(LVSP)、左心室舒张末压(LVEPD)、心肌细胞线粒体膜电位升高,且随着艾司洛尔组给药剂量的增加,心肌细胞凋亡指数、CK、LDH、心肌组织NF-κBmRNA和蛋白表达水平、TNF-α、IL-2、IL-6表达水平逐渐降低,LVSP、LVEPD、心肌细胞线粒体膜电位逐渐升高,剂量-效应关系明显(P<0.05)。结论艾司洛尔能降低心肌细胞凋亡指数,提高心肌细胞线粒体膜电位,进而减轻脓毒症大鼠心肌损伤程度,其机制与艾司洛尔能抑制炎症信号通路NF-κBmRNA、蛋白表达水平进而抑制炎性因子IL-2、IL-6、TNF-α的表达有关。

Objective To investigate the effects of esmolol on mitochondrial membrane potential and expression of nuclear factor kappa-B(NF-κB) in myocardial tissue of septic rats.Methods A total of 100 Sprague Dawley(SD) rats were selected, which aged 6 - 8 days,body mass was 110 - 150 g with mean body mass of 130.65 g.The rats were divided into 5 groups by random number table method: control group,model group,low dose-esmolol group(5.0 mg/kg),medium dose-esmolol group (10.0 mg/kg) and high-dose esmolol group(20.0 mg/kg).Rats in model group and different dose esmolol groups were made into sepsis models and were administered with the corresponding drugs.The control group and the model group were given an equal volume of 0.9 % sodium chloride solution(normal saline).Cardiac function index,cardiomyocyte apoptosis,myocardial mitochondrial membrane potential,NF-κB protein,mRNA level,interleukin(IL)-2,IL-6 and tumor necrosis factor-α(TNF-α) protein level after experiments were measured.Results Compared with model group,cardiomyocyte apoptosis index, creatine kinase(CK),lactate dehydrogenase(LDH),myocardial tissue NF-κB mRNA,protein expression level,TNF-α,IL-2 and IL-6 in each of esmolol dose group decreased,while left ventricular systolic pressure(LVSP),left ventricular end-diastolic pressure(LVEPD) and myocardial cell mitochondrial membrane potential increased.With the increase of esmolol dose,the expression of cardiomyocyte apoptosis index,CK,LDH,myocardial tissue NF-κB mRNA,protein expression,TNF-α,IL-2 and IL-6 decreased gradually,the mitochondrial membrane potential of LVSP,LVEPD and cardiomyocytes increased gradually, and the dose-effect relationship was significant(P < 0.05).Conclusion It is demonstrated that esmolol could decrease the apoptotic index and increase mitochondrial membrane potential of cardiomyocytes to alleviate the myocardial injury degree of septic rats.The mechanism is related to inhibition of mRNA and protein expression of inflammatory signaling pathway NF-κB,and expression levels of inflammatory factors IL-2,IL-6 and TNF-α.