雷公藤红素对大鼠心肌梗死后心电活动异常的影响及机制研究

Effects of celastrol on abnormal cardiac electrical activity in rats with myocardial infarction and its mechanism

目的探讨雷公藤红素对心肌梗死(myocardial infarction,MI)后大鼠心电活动的影响的保护作用及机制。方法将SD大鼠随机分为假手术(Sham)组、心肌梗死+生理盐水(MI)组、心肌梗死+雷公藤红素(MI+Cel)组,采用结扎冠状动脉的左前降支方法建立MI模型。MI造模成功后连续1月腹腔注射1 mg/kg雷公藤红素,假手术组和心肌梗死组注射等量生理盐水。1月后通过心脏超声检测心脏功能,记录心电图测量心率变异性(HRV)、低频(LF)、高频(HF)、QT间期、校正QT间期(QTc)和TpeakTend间期(Tp-e),测量心室心尖部(LVA)、心中部(LVM)和心底部(LVB)有效不应期(ERP),免疫荧光检测星状神经节(SCG)中C-fos,荧光定量、PCR检测心肌核因子E2、相关因子2(Nrf2)、血红素加氧酶-1(HO-1),生化法检测血清去甲肾上腺素(NE)、心肌超氧化物歧化酶(SOD)和丙二醛(MDA)的水平。结果与sham组比较,MI组SCG中C-fos相对表达量显著升高,NE水平明显升高(P<0.05),LF、LF/HF显著升高,HF显著降低,QT间期、QTc、Tp-e显著延长(P<0.05),心室LVA、LVM、LVB的ERP显著缩短,左室射血分数(LVEF)和左室短轴缩短率(LVFS)均下降,左室收缩期内径(LVIDs)和左室舒张末期内径(LVIDd)明显增高,心肌MDA水平显著升高,SOD的水平显著下降,心肌的Nrf2、HO-1 mRNA相对表达量明显降低(P<0.05)。与MI组比较,MI+雷公藤红素组SCG中C-fos相对表达量显著降低,血清NE水平明显下降(P<0.05),LF、LF/HF显著降低,HF显著升高,QT间期、QTc、Tp-e显著缩短(P<0.05),心室LVA、LVM、LVA的ERP显著延长,LVEF和LVFS均升高,LVIDd明显降低,心肌MDA水平显著降低,心肌SOD的水平显著升高,心肌的Nrf2、HO-1mRNA相对表达量明显增高(P<0.05)。结论雷公藤红素对心肌梗死后心脏功能及心电活动异常具有保护作用,可能通过抑制交感神经活性和降低氧化应激反应发挥作用。

Objective To investigate celastrol's protective effect and mechanism on cardiac electrical activity in rats with myocardial infarction(MI).Methods SD rats were randomly divided into the sham-operated group,an MI+saline group,and an MI+celastrol group.MI was induced by ligation of the left anterior descending branch of the coronary artery.After successful modeling of MI,celastrol 1 mg/kg was intraperitoneally injected for 1 month,and the sham operation group and MI group were injected with the same amount of normal saline.After 1 month,heart function was detected by echocardiography,and electrocardiogram was recorded to measure HRV(LF,HF),QT interval,corrected QT interval(QTc).TpeakTend interval(Tp-e),and effective refractory period(ERP)of ventricular apex(LVA),heart base(LVM)and heart base(LVB).The levels of C-fos in stellate ganglion(SCG)were detected by immunofluorescence,Nrf2 and HO-1 in myocardium were detected by qRT-PCR,and the levels of NE in serum and superoxide dismutase(SOD)and malondialdehyde(MDA)in myocardium were detected by biochemical methods.Results Compared with the sham group,the relative expression of C-fos in SCG was significantly higher in the MI group,serum norepinephrine(NE)levels were significantly higher(P<0.05),LF and LF/HF were significantly higher,HF was significantly lower,QT interval,QTc,and Tp-e were significantly prolonged(P<0.05),and the ERP of ventricular LVA,LVM,and LVB were significantly shortened.Left ventricular ejection fraction(LVEF)and left ventricular short-axis shortening(LVFS),left ventricular systolic internal diameters(LVIDs)and left ventricular end-diastolic internal diameters(LVIDd)were both decreased,myocardial MDA levels were significantly increased,SOD levels were significantly decreased,and myocardial relative expression of Nrf2,and HO-1 mRNAs was significantly decreased(P<0.05).Compared with the MI group,the relative expression of C-fos in SCG was significantly lower in the MI+celastrol group,the level of serum NE was significantly lower(P<0.05),the levels of LF and LF/HF were significantly lower,the level of HF was significantly higher,and the QT interval,QTc,and Tp-e were significantly shorter(P<0.05),and the ERP of ventricular LVA,LVM,and LVA were significantly prolonged,and the levels of EF and FS were higher(P<0.05).LVIDd was significantly lower,myocardial MDA level was significantly lower,myocardial SOD level was significantly higher,and relative expression of Nrf2 and HO-1 mRNA in the myocardium was significantly higher(P<0.05).Conclusion Celastrol has a protective effect on abnormal cardiac function and cardiac electrical activity after myocardial infarction,which may play a role by inhibiting sympathetic nerve activity and reducing oxidative stress response.