The purpose of this study was to investigate the potential cardioprotection roles of Rapamycin in anoxia/reoxygenation（A/R） injury of cardiomyocytes through inducing autophagy, and the involvement of PI3k/Akt pathwa...The purpose of this study was to investigate the potential cardioprotection roles of Rapamycin in anoxia/reoxygenation（A/R） injury of cardiomyocytes through inducing autophagy, and the involvement of PI3k/Akt pathway. We employed simulated A/R of neonatal rat ventricular myocytes（NRVM） as an in vitro model of ischemial/reperfusion（I/R） injury to the heart. NRVM were pretreated with four different concentrations of Rapamycin（20, 50, 100, 150 μmol/L）, and pretreated with 10 mmol/L 3-methyladenine（3MA） for inhibiting autophagy during A/R. Then, Western blot analysis was used to examine variation in the expression of LC3-Ⅱ, LC3-Ⅰ, Bim, caspase-3, p-PI3KⅠ, PI3KⅠ, p-Akt and Akt. In our model, Rapamycin had a preferential action on autophagy, increasing the expression of LC3-Ⅱ/ LC3-Ⅰ, whereas decreasing the expression of Bim and caspase-3. Moreover, our results also demonstrated that Rapamycin inhibited the activation of p-PI3KⅠ and enhanced the activation of p-Akt. It is concluded that Rapamycin has a cardioprotection effect by inducing autophagy in a concentration-dependent manner against apopotosis through PI3K/Akt signaling pathway during A/R in NRVM.展开更多
基金supported by grants from Natural National Science Foundation of China(No.81260023)National Science and Technology Infrastructure Program(No.2013BAI05B10)+1 种基金Graduate Innovation Special Fund of Jiangxi Province(No.YC2012-S029)Graduate Innovation Special Fund of Jiangxi Province(No.YC2014-B019)
文摘The purpose of this study was to investigate the potential cardioprotection roles of Rapamycin in anoxia/reoxygenation（A/R） injury of cardiomyocytes through inducing autophagy, and the involvement of PI3k/Akt pathway. We employed simulated A/R of neonatal rat ventricular myocytes（NRVM） as an in vitro model of ischemial/reperfusion（I/R） injury to the heart. NRVM were pretreated with four different concentrations of Rapamycin（20, 50, 100, 150 μmol/L）, and pretreated with 10 mmol/L 3-methyladenine（3MA） for inhibiting autophagy during A/R. Then, Western blot analysis was used to examine variation in the expression of LC3-Ⅱ, LC3-Ⅰ, Bim, caspase-3, p-PI3KⅠ, PI3KⅠ, p-Akt and Akt. In our model, Rapamycin had a preferential action on autophagy, increasing the expression of LC3-Ⅱ/ LC3-Ⅰ, whereas decreasing the expression of Bim and caspase-3. Moreover, our results also demonstrated that Rapamycin inhibited the activation of p-PI3KⅠ and enhanced the activation of p-Akt. It is concluded that Rapamycin has a cardioprotection effect by inducing autophagy in a concentration-dependent manner against apopotosis through PI3K/Akt signaling pathway during A/R in NRVM.
