Journal of Jilin University(Medicine Edition) ›› 2022, Vol. 48 ›› Issue (1): 74-81.doi: 10.13481/j.1671-587X.20220110

• Research in basic medicine • Previous Articles     Next Articles

Effect of overexpression of Bax inhibitor 1 on cardiomyocyte apoptosis in rats with acute myocardial infarction and its mechanism

Zhaohui WAN1,Liang ZENG1(),Hui ZHOU2   

  1. 1.Department of Emergency,Second Hospital,University of South China,Hengyang 421001,China
    2.Department of Emergency,Third Affiliated Hospital,University of South China,Hengyang 421900,China
  • Received:2021-05-18 Online:2022-01-28 Published:2022-01-17
  • Contact: Liang ZENG E-mail:tangs198905@163.com

Abstract: Objective

To explore the effect of overexpression of B-cell lymphoma-2(Bcl-2) associated X protein (Bax) inhibitor 1 (BI-1) on the cardiomyocyte apoptosis in the rats with acute myocardial infarction (AMI), and to clarify its mechanism.

Methods

A total of 60 rats were randomly divided into sham operation group, model group, empty adenovirus (Ad-NC) group and BI-1 adenovirus (Ad-BI-1) group; there were 15 rats in each group. Except for sham group, the rats in other groups were ligated in the left anterior descending coronary arteries to establish the AMI rat models. Meanwhile, the rats in Ad-NC group and Ad-BI-1 group were injected with adenovirus-packaged empty plasmid and BI-1 overexpression plasmid in the myocardial infarction area, respectively. The cardiac function parameters left ventricular ejection fraction (LVEF), left ventricular fraction shortening (LVFS), left ventricular end diastolic diameter (LVEDD) and left ventricular end systolic diameter (LVESD) values of the rats were detected 72 h after operation; TTC staining method was used to detect the percentages of myocardial infarction areas of the rats in various groups; TUNEL method was used to detect the apoptotic rates of cardiomyocytes of the rats in various groups; colorimetric method was used to detect the activities of Caspase-3 in myocardium tissue of the rats in various groups; RT-qPCR method was used to detect the expression levels of BI-1 mRNA of the rats in various groups; Western blotting method was used to detect the expression levels of BI-1, Bcl-2, Bax, and endoplasmic reticulum stress related proteins GRP78, IRE1, p-IRE1,JNK,p-JNK proteins in myocardium tissue of the rats in various groups;the ratios of the p-IRE1/IRE1 and p-JNK/JNK were calculated.

Results

Compared with sham operation group, the LVEF and LVFS of the rats in model group were significantly reduced (P<0.05),while the LVEDD and LVESD,the percentage of myocardial infarction area, the Caspase-3 activity in myocardium tissue, and the apoptodtic rates of cardiomocytes were increased (P<0.05), the expression levels of BI-1 mRNA and protein, and the expression levels of Bcl-2 protein in myocardium tissue of the rats in model group were significantly reduced (P<0.05), and the expression levels of Bax, and GRP78 and the ratios of p-IRE1/IRE1 and p-JNK/JNK were significantly increased (P<0.05).Compared with model group, the LVEF and LVFS of the rats in Ad-BI-1 group were significantly increased (P<0.05), while the LVEDD and LVESD were markedly decreased(P<0.05); the percentage of myocardial infarction area,the apoptotic rate of cardiomyocytes,and the Caspase-3 activity in myocardium tissue were decreased (P<0.05); the expression levels of BI-1 mRNA and protein and the expression level of Bcl-2 protein in myocardium tissue of the rats were significantly increased (P<0.05),and the expression levels of Bax and GRP78 and the ratios of p-IRE1/IRE1 and p-JNK/JNK were significantly decreased (P<0.05); the changes of the above indicators in Ad-NC group had no siginficant differences(P>0.05).

Conclusion

Overexpression of BI-1 reduces the level of cardiomyocyte apoptosis by inhibiting the endoplasmic reticulum stress pathway, thereby improving the cardiac function of the AMI rats.

Key words: Acute myocardial infarction, Apoptosis, Bax inhibitor 1, Endoplasmic reticulum stress, B-cell lymphoma-2 associated X protein

CLC Number: 

  • R542.22