Adenosine Attenuates LPS-Induced Cardiac Dysfunction by Inhibition of Mitochondrial Function via the ER Pathway

Figures

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  Figure 1. Effects of adenosine on heart function in LPS-induced septic rats as assessed by ultrasound. Female and male rats received LPS (10 mg/kg, i.p., 2 h) prior to gavage with different doses of adenosine. (a) Effects of different doses of adenosine on LVEF. (b) Effects of different doses of adenosine on LVFS. X ± SD, n = 8 rats per group, ∗P < 0.05, ∗∗P < 0.01 versus female model group; #P < 0.01, ##P < 0.01 versus male model group; &P < 0.05 versus male rats in each group.

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  Figure 2. Effects of adenosine on proinflammatory cytokine levels in LPS-induced septic rats as assessed by ELISA. Female and male rats received LPS (10 mg/kg, i.p., 2 h) prior to gavage with different doses of adenosine. (a) Effects of different doses of adenosine on TNF-α. (b) Effects of different doses of adenosine on IL-6. (c) Effects of different doses of adenosine on PCT. (d) Effects of different doses of adenosine on cTnI. X ± SD, n = 8 rats per group, ∗P < 0.05, ∗∗P < 0.01 versus female model group; #P < 0.01, ##P < 0.01 versus male model group; &P < 0.05 versus male rats in each group.

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  Figure 3. Effects of adenosine on the MAPK signaling pathway in LPS-induced septic rats as assessed by CBA. Female and male rats received LPS (10 mg/kg, i.p., 2 h) prior to gavage with different doses of adenosine. (a) Effects of different doses of adenosine on the phosphorylation of ERK. (b) Effects of different doses of adenosine on the phosphorylation of JNK. (c) Effects of different doses of adenosine on the phosphorylation of p38. X ± SD, n = 8 rats per group, ∗P < 0.05, ∗∗P < 0.01 versus female model group; #P < 0.01, ##P < 0.01 versus male model group; &P < 0.05 versus male rats in each group.

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  Figure 4. The antagonistic activity of ICI182,780 against adenosine on the mitochondrial swelling in LPS-stimulated H9c2 cells as assessed by FCM. H9c2 cells seeded on a 100 mm × 20 mm cell culture flask at a density of 2×105 cells/mL were treated with HQ (0.1 mg/mL) and adenosine (10 μM) for 24 h. In another experiment, the ER nonspecific antagonist Faslodex (ICI182,780, 1 μM) was added 30 min prior to HQ (0.1 mg/mL) and adenosine (10 μM) to evaluate whether the observed effects elicited by HQ and adenosine were mediated by the ER. Cells in each group were collected 24 h later and mitochondrial swelling was assessed. X ± SD, n = 3, ∗∗P < 0.01 versus model group (-ICI); &&P < 0.05 versus each group.

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  Figure 5. The antagonistic activity of ICI182,780 against adenosine on MMP (or ΔΨm) in LPS-stimulated H9c2 cells as assessed by FCM. H9c2 cells seeded on a 100 mm × 20 mm cell culture flask at a density of 2×105 cells/mL were treated with HQ (0.1 mg/mL) and adenosine (10 μM) for 24 h. In another experiment, the ER nonspecific antagonist Faslodex (ICI182,780, 1 μM) was added 30 min prior to HQ (0.1 mg/mL) and adenosine (10 μM) to evaluate whether the observed effects elicited by HQ and adenosine were mediated by the ER. Cells in each group were collected 24 h later and ΔΨm was assessed.

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  Figure 6. The antagonistic activity of ICI182,780 against adenosine on ROS production in LPS-stimulated H9c2 cells as assessed by FCM. H9c2 cells seeded on a 100 mm × 20 mm cell culture flask at a density of 2×105 cells/mL were treated with HQ (0.1 mg/mL) and adenosine (10 μM) for 24 h. In another experiment, the ER nonspecific antagonist Faslodex (ICI182,780, 1 μM) was added 30 min prior to HQ (0.1 mg/mL) and adenosine (10 μM) to evaluate whether the observed effects elicited by HQ and adenosine were mediated by the ER. Cells in each group were collected 24 h later and ROS levels were assessed. X ± SD, n = 3, ∗∗P < 0.01 versus model group (-ICI); &&P < 0.05 versus each group.