艾司洛尔对脓毒症大鼠心肌损伤的改善及对氧化还原酶及核因子-κB-P53的调控分析

Regulation of esmolol on oxidoreductase and NF-κB-P53 in the treatment of myocardial injury in septic rats

目的探讨艾司洛尔对脓毒症大鼠心肌损伤的改善及对氧化还原酶及核因子(NF)κB-P53的调控分析。方法SD大鼠100只,根据体质量随机分成5组:对照组、模型组、艾司洛尔组低、中、高剂量组、模型组、艾司洛尔各剂量组构建脓毒症大鼠心肌损伤模型,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%氯化钠注射液。试验结束后,检测大鼠心功能指标、大鼠心肌细胞组织氧化还原酶、NK-κB、P53mRNA、蛋白水平以及Caspase-3、Caspase-6、Caspase-9水平。结果与对照组比较,艾司洛尔各剂量左室收缩压(LVSP)、左室舒张末压(LVEPD)、超氧化物歧化酶(SOD)降低,肌酸激酶(CK)、乳酸脱氢酶(LDH)、丙二醛(MDA)、一氧化氮合酶(iNOS)、NF-κB、P53mRNA、蛋白表达水平、Caspase-3、Caspase-6、Caspase-9表达水平升高(P<0.05);与模型组比较,艾司洛尔各剂量LVSP、LVEPD、SOD升高,CK、LDH、MDA、iNOS、NF-κB、P53mRNA、蛋白表达水平、Caspase-3、Caspase-6、Caspase-9表达水平降低,且随着艾司洛尔组给药剂量的增加,LVSP、LVEPD、SOD逐渐升高,CK、LDH、MDA、iNOS、NF-κB、P53mRNA、蛋白表达水平、Caspase-3、Caspase-6、Caspase-9表达水平逐渐降低,剂量-效应关系明显(P<0.05)。结论艾司洛尔能降低心肌细胞氧化损伤反应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NK-κBmRNA、蛋白表达水平进而抑制凋亡因子P53、Caspase-3、Caspase-6、Caspase-9的表达有关。

Objective To investigate the regulation of esmolol on oxidoreductase and NF-κB-P53 in the treatment of myocardial injury in septic rats. Methods One hundred SD rats were randomly divided into 5 groups according to body weight: control group, model group, low-, medium-and high-dose esmolol groups. Rats were made into septic rat models with myocardial injury and received the corresponding treatments. At the end of the experiment, various indexes were also detected, including cardiac function indexes,oxidoreductase, mRNA and protein levels of NF-κB and P53, expression levels of Caspase-3, Cassase-6, and Cassase-9. Results The levels of LVSP, LVEPD, and SOD ranking in an ascending order was control group, low-, medium-and high-dose esmolol groups and model group (P<0.05), and the effect within esmolol dose groups had a dose-dependent manner (P<0.05). The levels of CK, LDH, MDA, iNOS, mRNA and protein levels of NFκB and P53 as well as expression levels of Caspase-3, Cassase-6, and Cassase-9 ranking in a descending order was control group, low-, medium-and high-dose esmolol groups and model group (P<0.05), and the effect within esmolol dose groups had a dose-dependent manner (P<0.05). Conclusion Esmolol can alleviate the oxidative damage of cardiomyocytes and the myocardial injury degree in sepsis rats. Its mechanism is related to the inhibition of mRNA and protein levels of NFκB as well as the inhibition of expression of apoptotic factors P53, Caspase-3, Caspase-6 and Caspase-9.