比索洛尔激活Nrf2/HO-1通路抑制氧化应激缓解急性心肌梗死大鼠心肌损伤

Bisoprolol inhibits oxidative stress and relieves myocardial injury via activating Nrf2/HO-1 pathway in rats with acute myocardial infarction

目的探索比索洛尔对急性心肌梗死大鼠氧化应激损伤的影响及可能机制。方法大鼠随机分为假手术组(Sham)、急性心肌梗死大鼠模型组(AMI)、比索洛尔治疗组(Bis)和比索洛尔+锌原卟啉9组(Bis+ZnPP),每组10只。造模后第8天,超声检测各组大鼠心功能;TTC染色后计算心肌梗死面积;HE和MASSON染色观察心肌损伤和纤维化程度;ELISA检测各组大鼠血清中磷酸肌酸激酶(CK)、磷酸肌酸激酶同工酶MB(CK-MB)、乳酸脱氢酶(LDH)含量、丙二醛(MDA)含量、超氧化物歧化酶(SOD)及谷胱甘肽(GSH-Px)含量;Western blot检测各组大鼠心肌中核因子E2相关因子2(Nrf2)及HO-1蛋白表达情况。结果比索洛尔显著提升心肌梗死大鼠缩短分数(FS%)及射血分数(EF%),降低左心室舒张末期内径(LVEDd)、左心室收缩末期内径(LVEDs)及左室舒张末期后壁厚度(LVPWd),减少心肌梗死面积,减轻心肌损伤,抑制纤维化,降低血清中CK、CK-MB、LDH含量,降低心肌组织中MDA含量,并升高SOD、GSH-Px活性,上调心肌中Nrf2与HO-1蛋白的表达(P<0.05)。而给予HO-1抑制剂ZnPP后,Bis的上述作用均被减弱或抑制。结论比索洛尔减轻急性心肌梗死大鼠氧化应激,与激活Nrf2/HO-1信号通路有关。

Objective To explore the effect and mechanism of bisoprolol on oxidative stress injury in rats with acute myocardial infarction. Methods Rats were randomly divided into sham operation group(Sham), acute myocardial infarction model group(AMI), bisoprolol treatment group(Bis), bisoprolol+zinc protoporphyrin 9 group(Bis+ZnPP), 10 animals per group. The cardiac function was detected by ultrasound, the area of ??myocardial infarction was calculated after TTC staining, the degree of myocardial injury and fibrosis was observed by HE and MASSON stainings. The content of serum creatine kinase(CK), phosphocreatine kinase isoenzyme MB(CK-MB), lactate dehydrogenase(LDH), malondialdehyde(MDA), superoxide dismutase(SOD) and glutathione peptide(GSH-Px) was detected by ELISA. The expression of Nuclear factor E2 related factor 2(Nrf2) and HO-1 in myocardium were detected by Western blot. Results Bisoprolol increased myocardial infarction shortened fraction(FS%) and ejection fraction(EF%), reduced left ventricular enddiastolic diameter(LVEDd) and left ventricular end-systolic diameter(LVEDs) and left ventricular end diastolic Wall thickness(LVPWd), reduced the area of myocardial infarction and myocardial damage, inhibited fibrosis, reduced contents of CK and CK-MB and LDH in serum, downregulated MDA content in myocardial tissue, but increased SOD and GSH-Px activity, increased the expression of Nrf2 and HO-1 protein in myocardium. After administration of the HO-1 inhibitor ZnPP, the above-mentioned effects of Bis were all weakened or inhibited. Conclusion Bisoprolol reduced oxidative stress in rats with acute myocardial infarction, which is related to the activation of Nrf2/HO-1 signaling pathway.