姜酮对急性心肌梗死大鼠心肌的保护作用及机制研究

Study on the protective effect and mechanism of zingerone on the myocardium of acute myocardial infarction rats

目的探究姜酮(ZGR)对急性心肌梗死后大鼠心肌的影响。方法2022年7—9月于武汉大学人民医院心血管病研究所进行实验。将雄性SPF级SD大鼠30只随机数字表法分为Sham组、心肌梗死(MI)组、MI+ZGR组,每组10只。MI+ZGR组、MI组分别以ZGR(6 mg·kg^(-1)·d^(-1))及等量生理盐水灌胃处理21 d,在药物处理第14天对冠状动脉的左前降支进行结扎造模,Sham组手术步骤相同但不结扎,并给予等量生理盐水灌胃;术后7 d行心脏超声检查左心室收缩末期内径(LVESD)、左心室舒张末期内径(LVEDD)、左心室短轴缩短率(LVFS)、左心室射血分数(LVEF);开胸取心脏组织行HE染色观察心脏病理改变;酶联免疫吸附法(ELISA)检测血清白介素-6(IL-6)、肿瘤坏死因子-α(TNF-α)及心肌组织超氧化物歧化酶(SOD)、丙二醛(MDA)水平;蛋白免疫印迹技术检测心脏组织中核转录因子红系2相关因子(Nrf2)、血红素氧合酶1(HO-1)、核因子κB(NF-κB)的表达水平。结果心脏超声检查显示,与MI组比较,MI+ZGR组大鼠的LVEDD、LVESD降低(F/P=45.21/<0.001、95.45/<0.001),LVEF、LVFS升高(F/P=61.13/<0.001、83.90/<0.001)。ELISA检测显示,与MI组比较,MI+ZGR组大鼠血清IL-6、TNF-α显著降低(F/P=237.40/<0.001、532.70/<0.001),心肌组织SOD显著升高(F/P=516.50/<0.001),MDA显著下降(F/P=105.90/<0.001)。HE切片显示,ZGR处理可以显著减轻MI大鼠炎性细胞的浸润,改善细胞肿胀程度。蛋白免疫印迹技术显示,与MI组比较,MI+ZGR组大鼠心肌组织Nrf2、HO-1蛋白表达水平显著升高(P<0.01),NF-κB蛋白水平显著降低(P<0.01)。结论ZGR处理可通过改善心肌梗死后的炎性反应及氧化应激水平来保护心功能。

Objective To explore the effect of zingerone(ZGR)on the myocardium of rats after acute myocardial infarction.Methods The experiment was conducted at the Institute of Cardiovascular Disease,People's Hospital,Wuhan University from July to September 2022.Thirty male SPF grade SD rats were randomly divided into Sham group,MI group,and MI+ZGR group using a number table method,with 10 rats in each group.The MI+ZGR group and MI group were treated with ZGR(6 mg·kg^(-1)·d^(-1))and an equal amount of physiological saline by gavage for 21 days,respectively.On the 14th day of drug treatment,the left anterior descending branch of the coronary artery was ligated.Cardiac ultrasound examination was performed 7 days after surgery.Open the chest and take the heart for HE staining to observe the pathological changes of the heart.Enzyme linked immunosorbent assay(ELISA)for detecting serum interleukin-6(IL-6)and tumor necrosis factor-α(TNF-α),and the levels of superoxide dismutase(SOD)and malondialdehyde(MDA)in myocardium.Protein immunoblotting technology was used for detecting nuclear transcription factor erythroid 2 related factor(Nrf2),heme oxygenase-1(HO-1),and nuclear factorκB(NF-κB)expression level in cardiac tissue.Results Cardiac ultrasound examination showed that compared with the MI group,the LVEDd and LVEDs of the MI+ZGR group rats significantly decreased(F/P=45.21/<0.001,95.45/<0.001),while LVEF and LVFS increased(F/P=61.13/<0.001,83.90/<0.001).ELISA detection showed that compared with the MI group,the serum IL-6 and TNF-αlevels in the MI+ZGR group of rats were significantly higher Significantly reduced(F/P=237.40/<0.001,532.70/<0.001),myocardial tissue SOD significantly increased(F/P=516.50/<0.001),and MDA significantly decreased(F/P=105.90/<0.001).HE slices showed that ZGR treatment can significantly reduce the infiltration of inflammatory cells and improve the degree of cell swelling in MI rats.Protein immunoblotting technology showed that compared with the MI group,the MI+ZGR group significantly increased the expression levels of Nrf2 and HO-1 proteins in the myocardial tissue of rats(P<0.01),and NF-κB protein level significantly decreased(P<0.01).Conclusion ZGR treatment can protect cardiac function by improving inflammation and oxidative stress levels after MI.