摘要
目的探讨金丝桃苷(Hyp)对主动脉弓缩窄所致心肌肥厚的保护作用及可能机制。方法主动脉缩窄术(TAC)建立心肌肥厚模型,将40只8周龄雄性C57BL/6J小鼠随机分为4组:假手术(Sham)组、TAC组、Hyp治疗TAC(Hyp+TAC)组和Hyp联合核因子E2相关因子2(Nrf2)抑制剂ML385治疗TAC(Hyp+ML385+TAC)组。术后4周,超声检测左室射血分数(LVEF)、左室短轴缩短率(LVFS)、左室舒张末期后壁的厚度(LVPWd);HE染色观察心肌横截面积;Masson染色检测心肌纤维化;计算心脏质量/体质量比(HW/BW);DHE染色观察活性氧(ROS)生成;qRT-PCR检测心房钠尿肽(ANP)、脑钠肽(BNP)和β-肌球蛋白重链(β-MHC)的mRNA表达;Western blot检测Nrf2、血红素氧合酶1(HO-1)、超氧化物歧化酶2(SOD2)、NADPH氧化酶2(gp91phox)蛋白表达;多组间差异采用单因素方差分析进行比较,两组间比较采用LSD-t检验。结果与Sham组比较,TAC组LVEF和LVFS值降低,LVPWD值增加(P<0.01),心肌细胞横截面积增大,心肌纤维化、HW/BW值以及ANP、BNP和β-MHC的mRNA表达增加(P<0.01),ROS生成和gp91phox的表达增多(P<0.01),而Nrf2、HO-1和SOD2表达减少(P<0.01);与TAC组比较,Hyp+TAC组心脏LVEF和LVFS值增加,LVPWD值降低(P<0.01),心肌细胞横截面积减小,心肌纤维化和HW/BW值均减小(P<0.01),ANP、BNP和β-MHC的mRNA表达减少(P<0.01),ROS生成和gp91phox的表达降低(P<0.01),而Nrf2、HO-1和SOD2的表达增加(P<0.01);然而,ML385能部分逆转Hyp对TAC心脏各指标的改善作用。结论Hyp可以通过抑制氧化应激和心肌纤维化,改善压力负荷所致心肌肥厚,其机制可能与调控Nrf2/HO-1信号有关。
Objective To investigate the protective effect of hyperoside(Hyp)on transverse aortic constriction-induced cardiac hypertrophy and its possible mechanism.Methods Forty 8-week-old male C57BL/6J mice were randomly divided into four groups:Sham group,TAC group,Hyp+TAC group and Hyp+ML385+TAC group.Four weeks after operation,cardiac function including left ventricular ejection fraction(LVEF),left ventricular fractional shortening(LVFS)and left ventricular end-diastolic posterior wall thickness(LVPWd)were measured with echocardiography.HE staining was used to evaluate the myocyte cross-sectional area.Masson staining was used to determine myocardial fibrosis.The ratio of heart weight/body weight was calculated.DHE staining was used to assess reactive oxygen species(ROS)production.The mRNA levels of atrial natriuretic peptide(ANP),brain natriuretic peptide(BNP)andβ-myosin heavy chain(β-MHC)were detected by qRT-PCR.The protein levels of NF-E2-related factor 2(Nrf2),heme oxygenase-1(HO-1),superoxide dismutase2(SOD2)and NADPH-Oxidase 2(gp91phox)were detected by Western blot.Differences among groups were compared by one-way analysis of variance,and LSD-t test was used for comparison between the two groups.Results Compared with the Sham group,the values of LVEF and LVFS in the TAC group decreased(P<0.01).The value of LVPWd,the cross-sectional area,fibrosis and the ratio of HW/BW increased(P<0.01).The mRNA levels of ANP,BNP andβ-MHC were upregulated(P<0.01).The ROS production and gp91phox protein level were elevated in the TAC group(P<0.01),while the protein levels of Nrf2,HO-1 and SOD2 decreased(P<0.01).Compared with the TAC group,the values of LVEF and LVFS in the Hyp+TAC group increased(P<0.01).The value of LVPWd,the cross-sectional area,fibrosis and the ratio of HW/BW decreased(P<0.01).The mRNA levels of ANP,BNP andβ-MHC were downregulated(P<0.01).The ROS production and gp91phox protein levels were reduced in the Hyp+TAC group(P<0.01),while the protein levels of Nrf2,HO-1 and SOD2 increased(P<0.01).However,ML385 could
作者
张晓东
张艳涛
张磊
董文婷
安慧仙
韩杨
张杰
刘治国
李炜
王伟
Zhang Xiaodong;Zhang Yantao;Zhang Lei;Dong Wenting;An Huixian;Han Yang;Zhang Jie;Liu Zhiguo;Li Wei;Wang Wei(Dept of Cardiology,Xi’an International Medical Center Hospital,Xi’an 710100)
出处
《安徽医科大学学报》
CAS
北大核心
2023年第12期2058-2063,共6页
Acta Universitatis Medicinalis Anhui
基金
陕西省重点研发计划(编号:2022SF-217、2023-YBSF-576)。
