The Regulation of AMPKα1/Nrf2/ HO-1 Pathway Mediated by Galantamine Hydrobromide Lycoremine in Myocardial Ischemia Reperfusion Rats

ZENG Fei, LI Qiang, ZENG Bian, LI Xi, HUANG Ke-li, YU Tao, TAN Jin

Abstract

 To investigate the effects of AMPKα1/Nrf2/heme oxygenase-1 (HO-1) pathway mediated by galantamine hydrobromide lycoremine (Gal) on endoplasmic reticulum stress apoptosis, myocardial apoptosis and fibrosis in rats with myocardial ischemia reperfusion (I/R).  Methods  A myocardial ischemia reperfusion injury rat model was established, and the rats were randomly divided into 5 groups: Control group, I/R model group, Gal 1 mg/kg group, Gal 2 mg/kg group and Gal 4 mg/kg group. Left ventricular ejection fraction (LVEF), left ventricular end-diastolic volume (LVEDV), left ventricular end-systolic volume (LVESV), left ventricular wall thickness (LVWT), and left ventricular short-axis shortening rate (FS) were detected by doppler ultrasound. Hematoxylin eosin staining was used to detect the pathological damage of myocardial tissue. The expression of Caspase-3 was detected by immunohistochemistry. Protein expression levels of CCAAT/enhancer-binding protein homologous protein (CHOP), cleaved Caspase-12, growth arrest and DNA damageinducible protein 34 (GADD34), immunoglobulin heavy-chain-binding protein (BiP), α-smooth muscle actin (α-SMA), Collagen Ⅰ, AMPKα1, Nrf2, and HO-1 were measured by western blot, and AMPK inhibitor Compound C was added for verification.   Results  Compared with the I/R model group, the grade of pathological damage of myocardial tissue in each group of Gal was improved, and cleaved Caspase-3 positive expression rate and Caspase-3 mRNA level were significantly reduced (P<0.05) as well. The results showed that LVWT, FS and LVEF in Gal 2 mg/kg and Gal 4 mg/kg groups were significantly increased (P<0.05), LVEDV and LVESV were significantly reduced (P<0.05) compared with I/R model group. CHOP, cleaved Caspase-12, α-SMA, Collagen Ⅰ, AMPKα1, Nrf2, HO-1 protein levels were significantly reduced (P<0.05), and GADD34 and BiP protein levels were significantly increased (P<0.05) in Gal 2 mg/kg and Gal 4 mg/kg groups.   Conclusion  The regulation of AMPKα1/Nrf2/HO-1 pathway mediated by Gal on endoplasmic reticulum stress apoptosis, myocardial apoptosis and fibrosis in myocardial ischemia reperfusion rats.

 

Keywords: Galantamine hydrobromide lycoremine, Myocardial ischemia reperfusion, Endoplasmic reticulum stress, AMPKα1/Nrf2/HO-1 pathways

 

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