Journal of Jilin University(Medicine Edition) ›› 2022, Vol. 48 ›› Issue (2): 364-373.doi: 10.13481/j.1671-587X.20220213

• Research in basic medicine • Previous Articles     Next Articles

Inhibitory effect of sufentanil on apoptosis of myocardial cells in myocardial ischemia-reperfusion injury rats and its mechanism

Zhihui ZHAO(),Xianghua BAI,Jinling HE,Weiqin DUAN,Min LIU,Shengmao ZHANG   

  1. Department of Anesthesiology,Inner Mongolia Autonomous Region Peopl’s Hospital,Hohhot 010017,China
  • Received:2021-07-21 Online:2022-03-28 Published:2022-05-10
  • Contact: Zhihui ZHAO E-mail:zzh19880101@126.com

Abstract: Objective

To explore the effect of sufentanil on the apoptosis of myocardial cells and the long non-coding RNA-MALAT1 (LncRNA-MALAT1) targeted extracellular signal-regulated kinase 1/2 (ERK1/2) signaling pathway in the myocardial ischemia-reperfusion injury(MIRI) rats, and to clarify the possible mechanism of sufentanil in the MIRI rats.

Methods

Thirty male SD rats were randomly divided into sham operation group, model group and sufentanil group, with 10 rats in each group. The MIRI model was prepared by ligation of the anterior descending branch of the left coronary artery (LAD). In sham operation group, only thorax of the rats was opened without ligation.The rats in sufentanil group were injected with sufentanil 1 μg?kg-1 through the tail veins 10 min before reperfusion,and the rats in sham operation group and model group were injected with the same amount of normal saline through the tail veins.The expression levels of LncRNA-MALAT1 in myocardium tissue of the rats in various groups were detected by real-time fluorescence quantitative PCR (RT-qPCR) and fluorescence in situ hybridization (FISH) methods; the apoptotic rates of cardiomyocytes of the rats in various groups were determined by TUNEL method; the expression levels of cysteine protease protein-3 (caspase-3),cleaved cysteine protease protein-3 (cleaved-caspase-3),B-cell lymphoma-2 (Bcl-2), Bcl-2 associated X protein(Bax),ERK1/2 and phosphorylated ERK1/2 (p-ERK1/2) proteins in myocardium tissue of the rats in various groups were detected by Western blotting method. The hypoxia-reoxygenation model of cardiomyocytes was constructed to simulate the MIRI in vivo, and the experiment was divided into control group, model group, sufentanil group, pcDNA-MALAT1 group (MALAT1 group), sufentanil+pcDNA-MALAT1 group (sufentanil+MALAT1 group). The expression levels of caspase-3, cleaved-caspase-3, Bax,Bcl-2, ERK1/2 and p-ERK1/2 in the H9C2 cells were detected by Western blotting method.

Results

The animal experiment results showed that compared with sham operation group, the LncRNA-MALAT1 expression level in myocardium tissue of the rats in model group, the apoptotic rate of cardiomyocytes, the expression levels of cleaved-caspase-3, and the ratio of Bax/Bcl-2 were increased significantly (P<0.05); the expression levels of p-ERK1/2 proteins were decreased significantly (P<0.05); compared with model group, the LncRNA-MALAT1 expression level in the myocardium tissue of the rats in sufentanil group, the apoptotic rate of cardiomyocytes, the expression level cleaved-caspase-3,and the ratio of Bax/Bcl-2 were decreased significantly (P<0.05); the expression levels of p-ERK1/2 proteins were increased significantly (P<0.05). The cell experiment results showed that compared with control group, the expression level of cleaved-caspase-3 and the ratio of Bax/Bcl-2 in the HPC2 cells in model group were increased significantly (P<0.05), and the expression levels of p-ERK1/2 proetins were decreased significantly (P<0.05); compared with model group, the expression level of cleaved-caspase-3 and the ratio of Bax/Bcl-2 in the HPC2 cells in the sufentanil group were decreased significantly (P<0.05), and the expression levels of p-ERK1/2 proteins were increased significantly (P<0.05); compared with MALAT1 group, the expression level of cleaved-caspase-3 and the ratio of Bax/Bcl-2 in the HPC2 cells in sufentanil+MALAT1 group were decreased significantly (P<0.05),and the expression levels of p-ERK1/2 proteins were increased significantly (P<0.05).

Conclusion

Sufentanil can attenuate the apoptosis of cardiomyocytes in the MIRI rats, and its mechanism may be related to the inhibition of LncRNA-MALAT1 to activate the ERK1/2 signaling pathway.

Key words: Sufentanil, Ischemia-reperfusion injury, Long non-coding RNA, Metastasis-associated lung adnecarcinoma transcript 1, Apoptosis, Extracellular signal regulated kinase 1, Extracellular signal regulated kinase 2

CLC Number: 

  • R971.2