摘要
目的探讨槲皮素对心肌缺血再灌注(MIRI)大鼠氧化应激反应和心电图的改善作用及对单磷酸腺苷活化蛋白激酶(AMPK)-结节性脑硬化复合物(TSC2)-雷帕霉素靶蛋白(mTOR)通路的调控机制。方法将60只大鼠随机分为假手术组、模型组、槲皮素低剂量组、槲皮素高剂量组、阳性药物组,每组12只,假手术组仅打开胸腔,其余各组大鼠建立心肌缺血再灌注模型。建模结束后,槲皮素低剂量组、槲皮素高剂量组、阳性药物组分别用25 mg/kg槲皮素、50 mg/kg槲皮素、3 mg/kg依达拉奉经尾静脉注射给药,假手术组及模型组分别用等量生理盐水尾静脉注射给药,每日1次,干预4周。分析各组心电图的变化情况;计算各组心肌梗死面积;苏木精-伊红(HE)染色观察心肌组织病理变化;凋亡细胞原位末端转移酶标记法(TUNEL)检测心肌细胞凋亡率;酶联免疫吸附法(ELISA)检测心肌组织活性氧(ROS)、超氧化物歧化酶(SOD)、丙二醛(MDA)含量;蛋白免疫印迹法(Western Blot)检测心肌组织AMPK、p-AMPK、TSC2、p-TSC2、mTOR及p-mTOR相对表达量。结果模型组出现明显心律失常,槲皮素低剂量组、高剂量组心律失常现象均有明显改善,且槲皮素高剂量组效果更好;与模型组比较,槲皮素低、高剂量组及阳性药物组心肌梗死面积、心肌细胞凋亡率均降低(P<0.05);与槲皮素低剂量组比较,槲皮素高剂量组及阳性药物组心肌梗死面积、心肌细胞凋亡率降低(P<0.05);与槲皮素高剂量组比较,阳性药物组心肌梗死面积、心肌细胞凋亡率均降低(P<0.05);HE染色显示:模型组心肌纤维排列紊,间隙变大且有断裂现象,细胞着色不均匀,核裂解消失;槲皮素低剂量组心肌细胞排列略整齐,间隙较大,有纤维断裂及核裂解现象存在;槲皮素高剂量组心肌纤维排列较整齐,间隙明显变小,无明显肥大现象;阳性药物组心肌纤维排列整齐,细胞着色均匀,心肌细胞无肥大现�
Objective To investigate the effects of quercetin(QU)on oxidative stress response and electrocardiogram in myocardial ischemia reperfusion(MIRI)rats,and the regulation mechanism of adenosine monophosphate activated protein kinase(AMPK)-tuberous sclerosis complex2(TSC2)-mammalian target of rapamycin(mTOR)pathway.Methods Sixty rats were randomly divided into sham operation group,model group,QU low-dose group,QU high-dose group,and positive drug group,with 12 rats in each group.The thoracic cavity of sham operation group was opened only,and myocardial ischemia-reperfusion model was established in other groups.After modeling,QU low-dose group,QU high-dose group and positive drug group were injected with 25 mg/kg quercetin,50 mg/kg quercetin and 3 mg/kg edaravone via tail vein,respectively.Sham operation group and model group were injected with the same amount of normal saline through tail vein,once a day,for 4 weeks.The changes of electrocardiogram in each group were analyzed.The area of myocardial infarction in each group was calculated.Hematoxylin-eosin(HE)staining was used to observe the pathological changes of myocardial tissue.TUNEL assay was used to detect the apoptosis rate of myocardial cells.The contents of reactive oxygen species(ROS),superoxide dismutase(SOD),and malondialdehyde(MDA)in myocardium tissue were determined by enzyme linked immunosorbent assay(ELISA).The relative expression levels of AMPK,p-AMPK,TSC2,p-TSC2,mTOR,and p-mTOR were detected by Western Blot.Results The model group showed obvious arrhythmia,and the arrhythmia of QU low-dose group and QU high-dose group were significantly improved,and the effect of QU high-dose group was better.Compared with model group,myocardial infarction area and myocardial cell apoptosis rate in QU low-dose,QU high-dose,and positive drug groups were decreased(P<0.05).Compared with QU low-dose group,myocardial infarction srea and myocardial cell apoptosis rate in QU high-dose group and positive drug group were decreased(P<0.05).Compared with QU high-dose group,myo
作者
宣学习
张宇
张华
张传西
袁义强
XUAN Xuexi;ZHANG Yu;ZHANG Hua;ZHANG Chuanxi;YUAN Yiqiang(The 7th People′s Hospital of Zhengzhou,Zhengzhou 450016,Henan,China)
出处
《中西医结合心脑血管病杂志》
2022年第5期848-853,共6页
Chinese Journal of Integrative Medicine on Cardio-Cerebrovascular Disease
基金
河南省医学科技攻关计划项目(No.2017T02096)。
关键词
心肌缺血再灌注损伤
槲皮素
氧化应激
心电图
单磷酸腺苷活化蛋白激酶
结节性脑硬化复合物
雷帕霉素靶蛋白
实验研究
myocardial ischemia reperfusion injury
quercetin
oxidative stress
electrocardiogram
adenosine monophosphate activated protein kinase
nodular sclerosis complex
mammalian target of rapamycin
experimental study
