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

Tan Wuping; Cheng Siyi; Huang Jiaxing; Qiu Qinfang; Jiang Hong; Zhou Xiaoya

doi:10.3969/j.issn.1674-4055.2024.09.04

Abstract：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.