大黄素激活Nrf2/ARE/HO-1信号通路对心肌缺血再灌注损伤大鼠心功能保护作用  

Protective effect of emodin on cardiac function in rats with myocardial ischemia reperfusion injury by activating Nrf2/ARE/HO-1 signaling pathway

作　　者：崔勤涛[1] 王俊华 刘晓晨[1] 王学惠[1] 马海英[1] 苏国宝[1] Cui Qintao;Wang Junhua;Liu Xiaochen(Cardiovascular Surgery Dept,The First Affiliated Hospital of Xinxiang Medical College,Xinxiang 453000)

机构地区：[1]新乡医学院第一附属医院心血管外科,新乡453000

出　　处：《安徽医科大学学报》2020年第6期894-900,共7页Acta Universitatis Medicinalis Anhui

基　　金：河南省二〇一八年科技发展计划项目(编号:182102310182)。

摘　　要：目的探究大黄素通过激活Nrf2/ARE/HO-1信号通路对心肌缺血再灌注损伤(MIRI)大鼠心功能的保护作用。方法大鼠随机分为假手术组、MIRI模型组、辛伐他汀40 mg/kg组、大黄素20、40、60 mg/kg组,建立大鼠MIRI模型。心电图检测左心室舒张末期压(LVEDP)、左心室收缩压(LVSP)、左室内压力变化最大上升/下降速率(±dp/dtmax),测量心肌梗死面积,生化分析仪检测血清肌酸激酶(CK)、乳酸脱氢酶(LDH)和肌钙蛋白(cTnI)浓度;HE染色观察心肌组织病理改变;免疫组化检测裂解型半胱天冬酶(cleaved Caspase-3)阳性细胞率;试剂盒检测髓过氧化物酶(MPO)、丙二醛(MDA)、超氧化物歧化酶(SOD)含量;Western blot检测核因子E2相关因子2(Nrf2)、血红素氧化酶1(HO-1)蛋白水平;另设假手术组、MIRI模型组、大黄素处理组、大黄素+ML385处理组,Nrf2抑制剂ML385处理大黄素+ML385组大鼠后,检测大鼠心功能、病理改变、氧化应激各指标的变化。结果与假手术组比较,MIRI模型组大鼠LVEDP、LVSP升高,±dp/dtmax降低,心肌梗死面积增加,血清CK、LDH、cTnI浓度升高,组织呈明显病理改变,cleaved Caspase-3阳性细胞率增加,MPO、MDA含量升高,SOD含量降低,Nrf2和HO-1蛋白水平升高。大黄素处理对心功能损伤发挥保护作用,Nrf2信号通路进一步激活;ML385处理抑制了大黄素对心功能的保护作用。结论大黄素可缓解MIRI损伤,其作用机制与Nrf2/ARE/HO-1信号通路的激活有关。Objective To investigate the protective effect of emodin on cardiac function in rats with myocardial ischemia-reperfusion injury(MIRI)by activating Nrf2/ARE/HO-1 signaling pathway.Methods Rats were randomly divided into Sham group,MIRI group,Positive control group,emodin 20,40,60 mg/kg group,then MIRI model of rats were established,ECG detection of left ventricular end-diastolic pressure(LVEDP),left ventricular systolic pressure(LVSP),maximal rise/fall rate of left ventricular pressure change(±dp/dtmax),myocardial infarct size was measured,biochemical analyzer was used to detect the concentration of serum creatine kinase(CK),lactate dehydrogenase(LDH)and troponin(cTnI),myocardial tissue pathological changes were observed by HE staining,cleaved Caspase-3 positive cell rate was detected by immunohistochemistry,the content of myeloperoxidase(MPO),malondialdehyde(MDA),Superoxide dismutase(SOD)was measured by kits,Western blot was used to detect the protein levels of nuclear factor E2 related factor 2(Nrf2)and heme oxygenase 1(HO-1).Then rats were randomly divided into Sham group,MIRI group,emodin group and emodin+ML385 group,rats in emodin+ML385 group were treated by Nrf2 inhibitor ML385,and changes of cardiac function,pathological changes,inflammation and oxidative stress were detected.Result Compared with Sham group,the rats in MIRI group had elevated LVEDP and LVSP,decreased±dp/dtmax,increased myocardial infarct size,increased serum CK,LDH,and cTnI concentrations,obvious pathological changes in tissues,and the positive cell rate of cleaved Caspase-3 increased,the MPO and MDA cotent increased,SOD content decreased,protein levels of Nrf2 and HO-1 increased.Emodin treatment played a protective role for cardiac function damage,Nrf2 signaling pathway was further activated.ML385 treatment significantly inhibited emodin induced protective effect of cardiac function.Conclusion Emodin can alleviate MIRI injury,and its mechanism is related to the activation of Nrf2/ARE/HO-1 signaling pathway.

关 键 词：大黄素 心肌缺血再灌注 核因子E2相关因子2 血红素氧化酶1 

分 类 号：R542.2[医药卫生—心血管疾病]