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    Bradykinin postconditioning protects rat hippocampal neurons after restoration of spontaneous circulation following cardiac arrest via activation of the AMPK/mTOR signaling pathway
  • Figure 2|Effect of bradykinin postconditioning on autophagosomes in the hippocampi of rats with restoration of spontaneous circulation, as detected by transmission electron microscopy.

    The amount of autophagosomes in the hippocampus was evaluated to determine the effect of BK postconditioning on neuronal autophagy in ROSC rats. As indicated by the transmission electron microscopy images shown in Figure 2, the ROSC group exhibited an increase in the amount of neuronal autophagosomes compared with the Sham group. The BK group exhibited an increase in the amount of neuronal autophagosomes compared with the ROSC group. The amount of neuronal autophagosomes in the CP + BK group remained unchanged, whereas the amount of neuronal autophagosomes in the Ra + BK group was increased compared with that seen in the BK group. These findings suggest that BK postconditioning can promote neuronal autophagy in ROSC rats.


    Figure 3|Effect of bradykinin postconditioning on hippocampal cell apoptosis in rats with restoration of spontaneous circulation, as detected by terminal deoxynucleotidyl transferase dUTP nick end-labeling staining.

    The number of hippocampal TUNEL-positive cells was calculated to determine the effects of BK postconditioning on apoptosis in ROSC rats. As the TUNEL staining showed, the ROSC group exhibited significantly more hippocampal TUNEL-positive cells compared with the Sham group (P < 0.01). The BK group demonstrated a significant decrease in the number of hippocampal TUNEL-positive cells compared with the ROSC group (P < 0.01). The CP + BK group showed a significant increase in the number of hippocampal TUNEL-positive cells compared with the BK group (P < 0.01), while the Ra + BK group showed a significant decrease in the number of hippocampal TUNEL-positive cells compared with the BK group (P < 0.01; Figure 3). These findings suggest that BK postconditioning can reduce neuronal apoptosis in ROSC rats.


    Figure 4|Effect of bradykinin postconditioning on the immunopositivity of AMPK/mTOR signaling pathway, autophagy-related proteins, and brain injury marker in rats with restoration of spontaneous circulation, as detected by immunohistochemistry. 

    The p-AMPK, p-mTOR, NBR1, p-62, LC3 and S100β immunopositivity was measured to determine the effect of BK postconditioning on the AMPK/mTOR signaling pathway, autophagy-related proteins, and brain injury marker expression in ROSC rats. As shown in Figure 4, the rats in the ROSC group showed a significant decrease in p-mTOR and p62 immunopositivity (both P < 0.01), a significant increase in S100β (P < 0.01), p-AMPK (P < 0.05), and LC3 (P < 0.01) immunopositivity, and no change in NBR1 immunopositivity (P = 0.192) compared with the Sham group. The BK group exhibited a significant decrease in p-mTOR, p62, and S100β immunopositivity (all P < 0.01), as well as a significant increase in p-AMPK (P < 0.05), NBR1 (P < 0.01), and LC3 (P < 0.01) immunopositivity compared with the ROSC group. The CP + BK group showed a significant decrease in LC3 (P < 0.01), p-AMPK (P < 0.01), and NBR1 (P < 0.05) immunopositivity and a significant increase in S100β, p62, and p-mTOR immunopositivity (all P < 0.01), while the Ra + BK group exhibited a significant increase in LC3 (P < 0.01), p-AMPK (P < 0.01), and NBR1 (P < 0.05) immunopositivity and a significant decrease in S100β, p62 (both P < 0.01) and p-mTOR (P < 0.05) immunopositivity compared with the BK group. These findings suggest that BK postconditioning can inhibit S100β expression in ROSC rat neurons, reduce nerve damage, activate the AMPK/mTOR signaling pathway, inhibit p62 expression, and increase the autophagy-related proteins NBR1 and LC3 expression to promote autophagy.


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  • 发布日期: 2022-03-19  浏览: 123
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