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Protective effect of Ciwujia Injection on heart failure after acute myocardial infarction in rats
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DOI   10.11656/j.issn.1672-1519.2023.12.15
Key Words   acute myocardial infarction;heart failure;Ciwujia Injection;cardiac function;Nrf2/HO-1 signaling pathway;oxidative stress
Author NameAffiliation
FENG Lingling Second Department of Geriatrics, Handan Central Hospital, Handan 056001, China 
CHEN Shujie Second Department of Geriatrics, Handan Central Hospital, Handan 056001, China 
CHE Wei Second Department of Geriatrics, Handan Central Hospital, Handan 056001, China 
Abstract
    [Objective] To investigate the protective effect and possible mechanism of Ciwujia Injection(CWJI) on myocardial tissue of rats with heart failure after acute myocardial infarction(HF-AMI). [Methods] The rat model with HF-AMI was established by ligation of the anterior descending branch of the left coronary artery,and model group,Captopril(CPT,10 mg/kg) group,CWJI low-dose(CWJI-L,15 mg/kg),medium-dose(CWJI-M,30 mg/kg),high-dose(CWJI-H,60 mg/kg) group,and the Sham group were set up,with 16 rats in each group. After 4 weeks of continuous administration once a day in each group,the cardiac function [left ventricular ejection fraction(LVEF),left ventricular short axis shortening rate(LVFS),maximum rate of rise and fall of left indoor pressure(+dp/dtmax,-dp/dtmax)]was detected by Doppler ultrasound and physiological signal acquisition system. The level of cardiac troponin(cTnI),angiotensin Ⅱ(AngⅡ) and aldosterone(ALD) in serum were determined by enzyme-linked immunosorbent assay(ELISA). The left ventricular myocardial hypertrophy index(LVHI) was calculated. The myocardial histopathological changes,apoptosis and tissue fibrosis were observed by HE,TUNEL or Masson staining,the mitochondrial ultrastructure changes was observed by transmission electron microscopy. The activity of total superoxide dismutase(T-SOD),glutathione peroxidase(GSH-Px) and the content of malondialdehyde(MDA),reactive oxygen species(ROS) were detected by spectrophotometry. The mRNA expression of nuclear factor E2-related factor 2(Nrf2) and heme oxygenase 1(HO-1) were detected by RT-PCR. The protein expression of Nrf2 and HO-1 were detected by Western Blot. [Results] Compared with the model group,the LVEF,LVFS,+dp/dtmax,-dp/dtmax,the level of cTnI,Ang Ⅱ,ALD in serum and LVHI in CPT group,CWJI-M,CWJI-H groups were significantly decreased(P<0.05). The myocardial histopathological changes,apoptosis and tissue fibrosis were significantly improved,and the apoptosis index(AI) and collagen volume fraction(CVF) were significantly decreased(P<0.05). The ultrastructural changes of myocardial cell mitochondria were significantly improved. The activity of T-SOD,GSH-Px in myocardial tissue were significantly increased,while the content of MDA,ROS were significantly decreased(P<0.05). The mRNA and protein expression of Nrf2,HO-1 were significantly increased(P<0.05). The above effects of CWJI were dose-dependent,and the effect of CWJI-H group on other indexes except LVFS was better than those of CPT group(P<0.05). [Conclusion] CWJI can alleviate myocardial tissue lesion,cell apoptosis,tissue fibrosis and mitochondrial ultrastructure lesion in rats with HF-AMI,and improve cardiac function,which may be related to activation of Nrf2/HO-1 signaling pathway and inhibition of oxidative stress.

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