Ivabradine protects rats against myocardial infarction through reinforcing autophagy via inhibiting PI3K/AKT/mTOR/p70S6K pathway

Figures

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  Figure 1.. Effect of ivabradine on LVSP, LVEDP, and ± dp/dtmax of MI rats. (a) Left ventricular systolic pressure (LVSP). (b) Left ventricular end diastolic pressure (LVEDP). (c) maximal ascending/descending rate of left ventricular pressure over time (± dp/dtmax). n = 6 rats/group. Data were expressed as mean ± SD; ##P < 0.01 vs Sham group; **P < 0.01 vs MI group; &P < 0.05, &&P < 0.01 vs MI+Iva group. Abbreviations: 3-MA, 3-methyladenine; Iva, ivabradine; MI, myocardial infarction; Rap, rapamycin

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  Figure 2.. Effect of ivabradine on infarction size and cardiomyocyte apoptosis of MI rats. (a) Representative images of 2,3,5-triphenyltetrazolium chloride (TTC) staining. (b) Quantitation of infarction size. (c) Representative images of terminal deoxynucleoitidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) assay. Black arrows indicated TUNEL-positive cardiomyocytes. n = 6 hearts/group. Data were expressed as mean ± SD; ##P < 0.01 vs Sham group; **P < 0.01 vs MI group; &&P < 0.01 vs MI+Iva group. Abbreviations: 3-MA, 3-methyladenine; Iva, ivabradine; MI, myocardial infarction; Rap, rapamycin

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  Figure 3.. Effect of ivabradine on TNF-α, IL-1β, and IL-6 production of MI rats. Serum concentration of TNF-α (a), IL-1β (b), and IL-6 (c). mRNA expression levels of TNF-α (d), IL-1β (e), and IL-6 (f) in myocardial tissues. n = 6 hearts/group. Data were expressed as mean ± SD; ##P < 0.01 vs Sham group; **P < 0.01 vs MI group; &&P < 0.01 vs MI+Iva group. Abbreviations: 3-MA, 3-methyladenine; Iva, ivabradine; MI, myocardial infarction; Rap, rapamycin

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  Figure 4.. Effect of ivabradine on autophagy function of MI rats. (a) Representative Western blot (WB) bands of LC3II/I. (b) Quantification of LC3II, as normalized to LC3I. (c) Representative immunohistochemistry (IHC) staining images of ATG-5. (d) Representative WB bands of p62, Beclin1, ATG-5 and ATG-7. Quantification of p62 (e), Beclin1 (f), ATG-5 (g) and ATG-7 (h), as normalized to β-actin. n = 6 hearts/group. Data were expressed as mean ± SD; ##P < 0.01 vs Sham group; **P < 0.01 vs MI group; &P < 0.05, &&P < 0.01 vs MI+Iva group. Abbreviations: 3-MA, 3-methyladenine; Iva, ivabradine; MI, myocardial infarction; Rap, rapamycin

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  Figure 5.. Effect of ivabradine on AKT/mTOR/p70S6K pathway of MI rats. (a) Representative WB bands of p-PI3K, PI3K, AKT and p-AKT. Quantification of p-PI3K (b) and PI3K (c), as normalized to β-actin. (d) Representative WB bands of mTOR, p-mTOR, p70S6K and p-p70S6K. Quantification of p-PI3K (e) and PI3K (f), as normalized to β-actin. n = 6 hearts/group. Data were expressed as mean ± SD; ##P < 0.01 vs Sham group; **P < 0.01 vs MI group; &P < 0.05 vs MI+Iva group. Abbreviations: 3-MA, 3-methyladenine; Iva, ivabradine; MI, myocardial infarction; Rap, rapamycin