Grape Seed Proanthocyanidin Extract Ameliorates Cardiac Remodelling After Myocardial Infarction Through PI3K/AKT Pathway in Mice

Figures

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  FIGURE 1. GSPE improved the survival rate and cardiac function of MI mice. (A) The survival rate of mice in the GEPE-treated group compared with the MI group (log-rank: p < 0.01). (n = 3 per group) (B) The heart/body weight ration of mice in different groups. (C) Representative M-mode echocardiographic images in short axis from each group, the relative indicators included are LVEF(%), FS(%), LVIDd(mm). Data analyzed are mean ± SD. *Significant difference compared with the control group, p < 0.05; significance compared with the MI group, p < 0.05. n = 3 per group.

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  FIGURE 2. GSPE improved the fibrosis in myocardial tissue and myocardial pathological changes of MI mice. (A) Representative image and analysis of infarct size by TTC staining, normal area is red, infarct area is white. (B) The contents of SOD and MDA the mice serum in different froup. (C) Pathological changes in HE-staining anf Masson staining of cardiac section. The inflammatory cells in HE staining have been marked with arrows. Data analyzed are mean ± SD. *Significant difference compared with the control group, p < 0.05; significant difference compared with the MI group, p < 0.05. n = 3 per group.

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  FIGURE 3. GSPE attenuated MI induced apoptosis and myocardial fibrosis by activating PIK/AKT pathway. (A) Effects of GSPE on the levels of Bax and Bcl-2 evaluated by Western blot analysis. (B) Effects of GSPE on the levels of Col-1, Col-3 and a-SMA evaluated by Western blot analysis. (C) Immunofluorescense staining of a-SMA. (D) Effects of GSPE treatment on cardiac levels of p-PI3K, PI3K, p-AKT and AKT evaluated by Western blot analysis. *Significant difference compared with the control group. p < 0.05; significant difference compared with the MI group, p < 0.05, n = 3 per group.

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  FIGURE 4. Inhibition of the PI3K/AKT pathway reversed the protective effect of GSPE on cardiac function in vivo. (A) Representative M-mode echocardiographic images in short axis from each group, the relative indicatiors included are LVEF(%), FS(%), LVIDd(mm) and LVIDs(mm). (B) Pathological changes in HE-staining and Masson staining of cardiac section. The inflammatory cells in HE staining have been marked with arrows. Data analyzed are mean SD. *Significant difference compared with the MI group, p < 0.05; significant difference compared with the MI + GSPE group, p < 0.05. n = 3 per group.

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  FIGURE 5. Inhibition of PI3K/AKT pathway can reverse the anti-apoptosis and anti-fibrosis effects of GSPE. (A) Effects of GSPE treatment on cardiac levels of p-PI3K, PI3K, p-AKT evaluated by Western blot analysis. (B) Effects of GSPE on the levels of Bax and Bcl-2 evaluated by Western blot analysis. (C) Effects of GSPE on the levels of Col-1, Col-3 and a-SMA evaluated by Western blot analysis. (D) Immunofluorescence staining of a SMS. *Significant difference comapred with the MI froup, p < 0.05; significant difference compared with the MI + GSPE group, p < 0.05. n = 3 per group.

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  FIGURE 6. GSPE reduced apoptosis in H9C2 cells under oxygen-glucose deprivation through PI3K/AKT pathway. (A) H9C2 cells were culture under hypoxia condition for different time, CCK8 assay was used to assess the cell viability. The appropriate GSPE concentration eas evaluated by CCK8 assay after the cells were cultured under glucose oxygen deptrivation for 24 hours. *Significant difference compared with the DMSO group, P < 0.05. (B) Effects of GSPE on the expression of Bax and Bcl-2 evaluated by Western blot analysis. (C) H9C2 cells in different treatment were stained by Annexin V-FITC/PI staining and then distinguished by flow cytometer. The cell apoptosis rate was quantified. (D) Effects of GSPE treatment on the H9C2 cells of p-PIK, PIK, p-AKT and AKT evaluated by Western blot analysis. Data analyzed are mean ± SD. *Significant difference compared with the DMSO group, p < 0.05; significant difference compared with the OGD group, p < 0.05. n = 3 per group.

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  FIGURE 7. Inhibition of PI3K/AKT pathway reversed the protective effect of GSPE on H9C2 cells. (A) Effects of GSPE treatment on the H9C2 cells of p-PI3K, PI3K, p-AKT and AKT evaluated by Western blot analysis. (B) Effects of GSPE on the expression of Bax and Bcl-2 evaluated by Western blot analysis. (C) H9C2 cells in different treatment were stained by Annexin V-FITC/PI staining and then distinguished by flow cytometer. Then cell apoptosis rate was quantified. *Significant difference compared with the OGD group, p < 0.05; significant difference compared with the OGD + GSPE group, p < 0.05. p = 3 per group.